George S Deepe
University Of Cincinnati
Project start date: 2011-02-15
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to George S Deepe
STUDIES OF H CAPSULATUM-REACTIVE MURINE T CELL CLONES
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI023017-03 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: The long-term objectives of this research proposal are to study the biology of T lymphocytes that are reactive with Histoplasma capsulatum. To facilitate these studies, murine T cell lines that recognize histoplasmin have been generated and more recently, these lines have been cloned. The surface phenotype of the cloned T cells will be determined by flow microfluorometry. The capacity of these T cells to proliferate in response to heterologous fungal antigens will be measured. The in vitro and in vivo immunoregulatory function of T cell clones will be determined as well as their ability to produce immunoregulatory factors. In addition, partial characterization of the component of histoplasmin that stimulates proliferation of cloned T cells will be examined. Attempts will be made to generate clonotypic antibodies to the cloned T cells. Both an antisera and a monoclonal antibody will be produced. Clonotypic antibodies will be tested for their capacity to modulate the proliferative response of cloned T cells to histoplasmin. Finally, clonotypic antibodies will be used to characterize partially the surface receptor on cloned T cells that recognizes Histoplasma capsulatum.
Keywords: BLOOD CELLS, T LYMPHOCYTES, FUNGI, ASCOMYCETES, HISTOPLASMA, IMMUNITY, CELLULAR, LEUKOCYTE ACTIVATION, TRANSFORMATION AND PROLIFERATION, IMMUNOLOGY, MICROBIAL, TISSUE (CELL) CULTURE, CLONE CELLS, BLOOD CELLS, T LYMPHOCYTES, HELPER, HYPERSENSITIVITY, DELAYED HYPERSENSITIVITY, IMMUNITY, CYTOKINES, LYMPHOKINES, INTERFERONS, IMMUNITY, CYTOKINES, LYMPHOKINES, INTERLEUKIN 2, IMMUNITY, CYTOKINES, LYMPHOKINES, MIGRATION INHIBITORY FACTOR, IMMUNITY, IMMUNOREGULATION, IMMUNOGENETICS, MAJOR HISTOCOMPATIBILITY COMPLEX (LOCUS), IMMUNOLOGICAL PREPARATIONS, MONOCLONAL ANTIBODIES, IMMUNOLOGY, ANTIBODIES, IMMUNOLOGY, ANTIGENS FUNGAL, IMMUNOLOGY, ANTIGENS, SURFACE ANTIGENS, MYCOSES, HISTOPLASMOSIS, RECEPTORS, ANTIGEN RECEPTORS T-LYMPHOCYTE, ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), CELL SORTING, LASER, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA), IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOLOGICAL TESTS
Project start date: 1985-12-01
Project end date: 1989-05-31
CHEMOKINE-CYTOKINE NEXUS IN FUNGAL IMMUNITY
George S Deepe, Professor
University Of Cincinnati, Sponsored Research Services, Cincinnati, Oh 45221
Grant 1R01AI083313-01A1 from National Institute Of Allergy And Infectious Diseases
Abstract: The dimorphic fungus, Histoplasma capsulatum (Hc) is endemic to the Midwestern and southeastern United States. Most infections are mild or asymptomatic. The organism establishes a latent state and can cause a life-threatening infection in immunocompetent or immunosuppressed individuals. We have shown that the chemokine receptor, CCR2, is critically important in controlling pulmonary infection with Hc in mice. The absence of this receptor is associated with exacerbation of infection and the induction of interleukin (IL)-4 by unconventional sources-macrophages and dendritic cells. Neutralization of IL-4 restores immunity. We have obtained evidence that signaling by the chemokines CCL7 and 2, two CCR2 ligands, are important in optimal host defenses. In the following proposal, we will explore the mechanisms by which CCR2 signaling is important in constraining IL-4 generation and promoting an effective cellular immune response. Specific aim 1 will examine the role of CCL2 and 7 in host defenses and inflammation. We will identify the cells producing these chemokines in situ and ex vivo. We will investigate if the absence of the receptor or the chemokines alters the in vivo residence of yeast cells. We will ascertain if CCR2 ligands manifest a direct or indirect activation of phagocytes. In specific aim 2, we will utilize a mouse that has green fluorescent protein linked to the IL-4 gene to investigate the evolution and temporal appearance of IL-4- transcribing cells. Studies will be performed to determine if Hc modulates expression of CCR2. We also will investigate the pathways that macrophages and dendritic cells utilize to generate IL-4. In specific aim 3, we will examine mechanisms by which the absence of CCR2 and/or IL-4 contributes to defective immunity. We will assess the possibility that the absence of CCR2 promotes the emergence of alternatively activated macrophages or myeloid suppressor cells. We will determine if either or both of these populations dampen antifungal immunity. We will test T cell function and expansion. We will assess the possibility that the failure of T cells to expand in the lungs is consequence of active inhibition as well as modulation of surface receptors. The goal of these studies is to better understand the pathogenesis of Hc, thereby enhancing knowledge of how Hc escapes host defenses. These findings contribute to the influence of the chemokine- cytokine network in microbial pathogenesis and evince a new role for CCL7. This grant seeks to understand the interaction between two types of soluble mediators known as chemokines and cytokines in host resistance to a fungus that causes human disease, Histoplasma capsulatum. This fungus which is found world-wide is a serious cause of lung infection in both normal humans and those who have impaired immunity. Our work will demonstrate how important it is for appropriate signaling through a surface receptor for a particular chemokine in order that the host can survive
Keywords: Abbreviations; Antifungal Agents; Antifungal Drug; Appearance; B cell activating factor; B cell growth factor; B-Cell Differentiation Factor-1; B-Cell Growth Factor-1; B-Cell Growth Factor-I; B-Cell Proliferating Factor; B-Cell Stimulating Factor; B-Cell Stimulating Factor-1; B-Cell Stimulation Factor-1; B-Cell Stimulatory Factor 1 Gene; B-Cell Stimulatory Factor-1; BAF; BCDF-1; BCGF; BCGF-1; BCSF 1; BSF-1; BSF-1 Gene; BSF1; BSF1 (B cell stimulating factor 1); BSF1 Gene; Basophilic Granulocyte; Basophilic Histiocyte; Basophilic Leukocyte; Basophils; Basophils, Tissue; Binding; Binding (Molecular Function); Binetrakin; Blood Basophil; Blood Neutrophil; Blood Polymorphonuclear Neutrophil; Blood Segmented Neutrophil; Blood granulocytic cell; Bone Marrow; C-C Chemokines; CC chemokine receptor 2; CCL2; CCL2 gene; CCL7; CCL7 gene; CCL8; CCL8 gene; CCR2 protein; CIS protein; CIS-1 Protein; CISH; CISH Protein; Cachectin; Cachectin-Tumor Necrosis Factor; Cell Communication and Signaling; Cell Function; Cell Lineage; Cell Process; Cell Signaling; Cell physiology; Cells; Cellular Function; Cellular Physiology; Cellular Process; Chemokines, CC; Colony-Stimulating Factors; Colony-forming units; Communicating Junction; Cytofluorometry, Flow; Cytokine Inducible SH2-Containing Protein; Cytokine Network; Cytokine Network Pathway; Cytokine-Inducible Inhibitor of Signaling Type 1B; Cytokines, Chemotactic; Data; Defect; Dendritic Cells; Dysfunction; Endogenous Nitrate Vasodilator; Endothelium-Derived Relaxing Factor; Evolution; FLR; Failure (biologic function); Fatal Outcome; Flow Cytofluorometries; Flow Cytometry; Flow Microfluorimetry; Fluorescence; Functional disorder; Fungicides, Therapeutic; G18; GDCF-2; GDCF-2 HC11; GFP; Gap Junctions; Generations; Goals; Grant; Granular Leukocytes; Granulocytic cell; Green Fluorescent Proteins; HC11; HC14; Heterophil Granulocyte; Histocompatibility Complex; Histocompatibility Complices; Histoplasma capsulatum; Homologous Chemotactic Cytokines; Host Defense; Host resistance; Human; Human, General; IFN; IL-4; IL-4 Gene; IL4; IL4 Protein; IL4 gene; INFLM; Immune; Immune response; Immunity; Immunocompetent; Immunocompromised; Immunocompromised Host; Immunocompromised Patient; Immunosuppressed Host; In Situ; In Vitro; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Intercrines; Interferons; Interleukin-4; Interleukin-4 Gene; Interleukin-4 Precursor; Interleukin-4 Precursor Gene; Interleukins; Intracellular Communication and Signaling; Intravenous; Investigation; Knowledge; Life; Ligands; Link; Low-resistance Junction; Lung; Lymphocyte Stimulatory Factor 1; MARC; MCAF; MCGF-2; MCP-1; MCP-2; MCP-3; MCP1; MCP2; MCP3; MGC9434; MGI-1 Protein; Major Histocompatibility Complex; Major Histocompatibility Complices; Mammals, Mice; Man (Taxonomy); Man, Modern; Marrow Basophil; Marrow Mast Cell; Marrow Neutrophil; Mast Cell Growth Factor-2; Mediator; Mediator of Activation; Mediator of activation protein; Mice; Microfluorometry, Flow; Moab, Clinical Treatment; Molecular; Molecular Interaction; Monoclonal Antibodies; Monocyte Chemoattractant Protein-1; Monocyte Chemoattractant Proteins; Monocyte Chemotactic Protein 3; Monocyte Chemotactic Protein-1; Monocyte Chemotactic Proteins; Monocyte Chemotactic and Activating Factor; Monocyte Chemotactic and Activating Protein; Monocyte Secretory Protein JE; Mononitrogen Monoxide; Murine; Mus; Myelogenous; Myeloid; Myeloid Cell-Growth Inducer; NC28; Neutrophilic Granulocyte; Neutrophilic Leukocyte; Nexus; Nexus Junction; Nitric Oxide; Nitric Oxide, Endothelium-Derived; Nitrogen Monoxide; Nitrogen Protoxide; Nitrogen oxide; Organism; PCR; Pathogenesis; Pathway interactions; Phagocytes; Phagocytic Cell; Physiopathology; Polymerase Chain Reaction; Polymorph; Polymorphonuclear Cell; Polymorphonuclear Leukocytes; Polymorphonuclear Neutrophils; Population; Predisposition; Property; Property, LOINC Axis 2; Receptor Protein; Relative; Relative (related person); Research; Respiratory System, Lung; Reticuloendothelial System, Bone Marrow; Role; SCYA10; SCYA2; SCYA7; SCYA8; SIS cytokines; SMC-CF; SOCS; Signal Transduction; Signal Transduction Systems; Signaling; Small Inducible Cytokine A2; Small Inducible Cytokine A7; Small Inducible Cytokine A8; Source; Southeast U.S.; Southeast US; Southeastern United States; Subcellular Process; Suppressor Cells; Suppressor of Cytokine Signaling; Suppressor-Effector T-Lymphocytes; Surface; Susceptibility; T Suppressor Cell; T-Cell Growth Factor 2; T-Cells; T-Cells, Suppressor-Effector; T-Lymphocyte; T-Lymphocytes, Suppressor-Effector; TNF (unspecified); TNF Receptor Ligands; TNF-alpha; Testing; Thymus-Dependent Lymphocytes; Time; Tumor Necrosis Factor; Tumor Necrosis Factor Family Protein; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Veiled Cells; Work; Yeasts; amebocyte; anti-fungal; antifungals; beta-Chemokines; biological signal transduction; chemoattractant cytokine; chemokine; chemokine (C-C motif) ligand 8; chemokine receptor; cytokine; endothelial cell derived relaxing factor; failure; flow cytophotometry; fungus; granulocyte; host response; human disease; immunoresponse; immunosuppressed; immunosuppressed patient; in vivo; intraperitoneal; living system; macrophage; mast cell; mastocyte; microbial; monocyte chemoattractant protein-2; monocyte chemoattractant protein-3; monocyte chemotactic activating factor 3; monocyte chemotactic activating factor-2; monocyte chemotactic protein-2; neutrophil; pathophysiology; pathway; public health relevance; pulmonary; receptor; receptor 2, CC chemokine; residence; social role; suppressor T lymphocyte; thymus derived lymphocyte; tumor necrosis factor (unspecified); unspecified interleukin
Relevance: This grant seeks to understand the interaction between two types of soluble mediators known as chemokines and cytokines in host resistance to a fungus that causes human disease, Histoplasma capsulatum. This fungus which is found world-wide is a serious cause of lung infection in both normal humans and those who have impaired immunity. Our work will demonstrate how important it is for appropriate signaling through a surface receptor for a particular chemokine in order that the host can survive
Project start date: 2010-02-01
Project end date: 2015-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-070
1R01AI083313-01A1 (2010): $392500
IMMUNOPATHOGENESIS IN HISTOPLASMOSIS
George S Deepe, Professor
University Of Cincinnati, Sponsored Research Services, Cincinnati, Oh 45221
Grant 3R01AI073337-02S1 from National Institute Of Allergy And Infectious Diseases
Abstract: The dimorphic fungus, Histoplasma capsulatum (Hc) is endemic to the Midwestern and southeastern United States. Most infections are mild or asymptomatic. The organism establishes a latent state and can cause a life-threatening infection in immuno- suppressed individuals. We have shown that pulmonary infection with Hc in mice induces apoptosis of CD45+ lung leukocytes; apoptosis is controlled largely by tumor necrosis factor (TNF)-1 and Fas-Fas ligand interaction. Inhibition of apoptosis induced by neutralization of TNF-1 or Fas-Fas ligand interruption worsens the severity of infection. Inhibiting the activation of caspases, which are proteases involved in the apoptotic cascade, exacerbates infection. The aggressive nature of Hc in mice given an icaspase inhibitor is associated with elevations in interleukins 4 and 10. Each cytokine independently regulates the protective immune response in mice given the inhibitor. The effect of the caspase inhibitor is principally mediated by its effect on apoptosis and not an apoptosis-independent effect. We hypothesize that limited apoptosis is salutary for host defenses to Hc. In the following proposal, we will explore the mechanisms by which apoptosis contributes to protective immunity to Hc. Specific aim 1 will examine the cellular sources of interleukins 4 and 10, and the kinetics of production by cell populations in mice given a caspase inhibitor. We will examine if phagocytes or T cells or both produce one or more of these cytokines. We will determine if the pathways for apoptosis are similar among these populations. The second aim seeks to determine the functional consequences of apoptosis inhibition on human and mouse phagocyte function. We will examine the impact of caspase inhibition on nitric oxide release and on interleukins 4 and 10 release, and fungal handling by human and mouse phagocytes. We will examine if inoculum size modulates apoptosis of phagocytes. In aim 3, we will determine the impact of inhibition of apoptosis on T cell function. We will examine if inhibition of apoptosis alters antigen recognition by T cells, skews the T cell receptor repertoire, prevents CD8+ cell activation, or leads to the emergence of T cells that can suppress immunity. The goal of these experiments is to better understand the immunopathogenesis of Hc, thereby enhancing knowledge of how Hc escapes host defenses. This grant seeks to understand how the death of lymphocytes and macrophages modulates the expression of immunity to a fungus that causes human disease, Histoplasma capsulatum. This fungus which is found world-wide is a serious cause of lung infection in both normal humans and those who have impaired immunity. Our work will demonstrate how important it is for lymphocytes and macrophages to die in order that the host can survive
Project start date: 2008-06-01
Project end date: 2013-05-31
Budget start date: 1-JUN-2009
Budget end date: 31-MAY-2010
PFA/PA: PA-07-070
3R01AI073337-02S1 (2010): $48123
5R01AI073337-03 (2010): $386100
5R01AI073337-02 (2009): $390000
Protective Antigens From Histoplasma Capsulatum
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 2R01AI034361-11 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Protective immunity to the pathogenic fungus, Histoplasma capsulatum (Hc), requires collaboration between T cells and professional antigen presenting cells such as macrophages and dendritic cells. T cells exert a crucial role in host resistance by releasing cytokines that arm phagocytes to express anti-Hc activity. We reported that one antigen from Hc, recombinant heat shock protein (rhsp) 60, is immunogenic in murine models of histoplasmosis. We also have shown that the protective activity of this antigen requires the presence of CD4+, Vbeta8.1/8.2+ T cells and interferon-gamma, and interleukins-10 and 12 during the inductive phase of vaccination. In the efferent phase, interleukin-12 and interferon-gamma are required as well as CD4+ and CD8+ cells. Protection conferred by rhsp 60 is mediated by a domain spanning amino acids 172-443, and the effect of this polypeptide is dependent on the presence of Vbeta6+ cells and IFN-gamma. Furthermore, our preliminary data indicate that effect of rhsp 60 as vaccine persists for greater than or equal too 3 months and sustaining its durability requires tumor necrosis factor (TNF)-alpha and granulocyte-macrophage colony stimulating factor (GM-CSF) but not interleukins-10 or -12 or interferon-gamma. These data indicate that the requirements for maintaining effectiveness of rhsp 60 shift following the termination of vaccine delivery. The hypotheses are 1) the protective action of rhsp 60 is localized to a peptide, 2) the lack of endogenous IL-10 alters efficacy of rhsp 60 by subverting the generation of either cellular or molecular mediators of protection, and 3) the durability of rhsp 60 vaccination is dependent on TNF-alpha and GM-CSF and that the absence of these cytokines alters the mediators of protection. In this proposal we will pursue three specific aims intended to enhance knowledge regarding the mechanisms of vaccine efficacy using rhsp 60 as a model antigen. In the first aim, we will endeavor to identify a peptide within the protective domain, known as F3 that spans amino acids 172-443. We will seek to determine if a peptide can mimic the activity of F3, if protective T cells emerge and if interleukin-4 may be required for the Th1 response. In addition, we will ask if the peptide can mediate protection in a host with a biased Th2 phenotype. In the second aim, we will seek to understand how IL-10 contributes to vaccine efficacy. We will pursue the possibility that the absence of IL-10 alters cytokine production, antigen presenting cell function, T cell repertoire, and/or the generation of memory/effectors cells. In aim 3, we will examine how the absence of TNF-alpha and GM-CSF alters the durability of the efficacy of rhsp 60 as a vaccine. We will determine if the absence of either of these cytokines alters production of cytokines necessary for protection or causes up regulation of cytokines involved in exacerbating disease. We also will examine if their absence causes alterations in the emergence of protective T cells and/or memory/effectors cells. These studies should provide new insights into the mechanisms that underpin the efficacy of a vaccine. rhsp 60 serves as a paradigm, and the data emerging from this proposal may be broadly applicable to other antigens against intracellular pathogens.
Keywords: Histoplasma capsulatum, antigen presentation, cellular immunity, fungal antigen, heat shock protein, host organism interaction, immunogenetics, microorganism immunology, active immunization, colony stimulating factor, cytokine, helper T lymphocyte, interleukin 10, interleukin 4, protein localization, protein structure function, tumor necrosis factor alpha, enzyme linked immunosorbent assay, flow cytometry, gene targeting, immunization, laboratory mouse, molecular cloning, monoclonal antibody, transgenic animal
Project start date: 1993-07-01
Project end date: 2007-12-31
2R01AI034361-11 (2003): $189981
George S Deepe, Professor
University Of Cincinnati
sponsored Research Services
cincinnati, Oh 45221
Grant 5P01AI061298-050003 from National Institute Of Allergy And Infectious Diseases IRG: ZAI1
Abstract: Protective immunity to Histoplasma capsulatum requires the interaction of T cells with macrophages and dendritic cells. The human immune response to this fungus is effective at limiting infection, but not at sterilizing tissues. Once infected, the yeast may remain dormant for years within granulomas or other niches. When the integrity of the human immune system is breached, either by other infections such as human immunodeficiency virus or by pharmacologic agents that suppress immunity, the organism may escape the confines of the granuloma and replicate. This form is known as reactivation histoplasmosis and may be associated with life-threatening progressive infection if not promptly diagnosed and treated. The mechanisms that permit the organism to evade confinement are unknown. We have developed a murine model of reactivation histoplasmosis that will enable us to understand the perturbations in immunity that create a favorable environment for the organism to escape host defense mechanisms. C57BL/6 mice are infected with a nonlethal inoculum of yeast and at 42 days postinfection, when organisms are no longer detected by routine culture methods, mice are depleted of CD4+ and CD8+ cells. The loss of these cells, but not the individual subpopulation alone, is accompanied by a growth of the organism from both lungs and spleens. The infection becomes persistent over the next 46 days. We also have shown that the absence of B cells enhances the severity of reactivation. Unlike B cell sufficient mice, depletion of CD4+ cells in B cell knockout mice induces reactivation. Thus, the development of this model has permitted us to begin to explore the immunologic defects that are associated with this extremely important form of histoplasmosis. In the following proposal we will address two aims 1) To determine the immunological mechanisms that modulate reactivation. Specific projects include a) To determine the molecular constituents produced by CD4+ and/or CD8+ cells from lungs and spleens that prevent reactivation, b) To elucidate the immunologic elements that prevent reactivation from becoming progressive, c) To determine the contribution of B cells to reactivation, d) To examine the interaction between B cells and CD8 + cells, and e) To determine if the absence of transporter associated with antigen processing alters reactivation in mice. Specific Aim 2) To determine the influence of Th 1 and 2 immunity on reactivation. Specific projects include a) To determine if a preexisting bias in Th 2 immunity increases severity of reactivation, b) To determine if mice with an induced Th 2 response manifest enhanced severity of reactivation, c) To determine if age influences reactivation, d) To determine if a preexisting bias in Th 1 immunity modulates reactivation, e) To determine if the absence of B ceils alters reactivation in mice with a preexisting bias in Th 1or 2 immunity, and f) To determine the influence of corticosteroids on the reactivation process. Knowledge gained will advance our ability to prevent and/or treat this form of histoplasmosis
Keywords: B lymphocyte, Histoplasma, cell cell interaction, cellular immunity, cytotoxic T lymphocyte, helper T lymphocyte, histoplasmosis, macrophage, pathologic process age difference, antigen presentation, corticosteroid, granuloma, immunodeficiency flow cytometry, laboratory mouse
Sponsored Links Excellgen http://Excellgen.com
DEFENDING AGAINST SYSTEMIC MYCOSES
George S Deepe, Professor
University Of Cincinnati, Sponsored Research Services, Cincinnati, Oh 45221
Abstract: Infection with the systemic fungi, Histoplasma capsulatum and Blastomyces dermatitidis afflict a large proportion of the population of the United States. H. capsulatum is the leading cause of fungal respiratory disease within the U.S. Both organisms are prevalent in the southeastern and Midwestern U.S., and they continue to take a toll on the health of the population at risk. It is unlikely that either of these will be controlled through public health measures since they are environmental fungi whose niches are difficult to detect. This proposal entitled "Defending Against Systemic Mycoses" represents a collaborative and synergistic effort among 4 laboratories in three institutions. The four principal investigators have a long-standing interest in the study of either or both of these fungi. Their combined research experience exceeds 70 years. Although located in different institutions, they have collaborated informally and formally on many occasions. Examples of the latter include co-authored manuscripts and shared NIH grants. The focus of this proposal will be to unearth the basic mechanisms of host response and fungal survival in order to create new and exciting means to prevent and/or treat these vexing microbial pathogens. Four projects are presented in this proposal. Dr. Deepe is the PI of the MRU and will be responsible for all the scientific performance of the grant. Project 1, led by Dr. Simon Newman, will determine the influence of cyclophilin as a ligand on H. capsulatum yeast for dendritic cells and to examine the role that this fungal molecule may play in modulating phagocyte biology including dendritic cells. Project 2 is headed by Dr. Bruce Klein, who will examine the novel observation that vaccination with a Bad1 mutant of B. dermatitidis or viable H. capsulatum can protect mice that lack CD4+ cells. This exciting finding suggests that immunosuppressed individuals, especially those who lack this cell population or in whom this cell population is dysfunctional, can be immunized against these pathogenic fungi. Project 3 headed by Dr. Deepe will examine the immunologic mechanisms that underpin reactivation histoplasmosis. This form of infection is thought to be one of the important means by which immunosuppressed as well as immunocompetent individuals develop progressive infection. Dr. Deepe has created a mouse model of reactivation disease and has demonstrated that B cells may exert a pivotal influence on the severity of reactivation. Project 4 is led by Dr. William Goldman, who has provided many new insights into the molecular biology of H. capsulatum. In this proposal he will examine the contribution of alpha (1,3) glucan to the virulence of H. capsulatum. His work will seek to understand the regulation of genes involved in synthesis of this moiety and the ability of this molecule to be a fungal drug target. The collaborative and synergistic effort manifested by this group of investigators will provide new and exciting information regarding prevention and/or treatment of these problematic fungi
Keywords: No Project Terms available
Project start date: 2004-06-01
Project end date: 2010-05-31
Budget start date: 1-JUN-2008
Budget end date: 31-MAY-2010
PFA/PA: RFA-AI-03-021
5P01AI061298-05 (2008): $0
5P01AI061298-04 (2007): $754826
5P01AI061298-03 (2006): $754932
5P01AI061298-02 (2005): $750578
1P01AI061298-01 (2004): $755466
PROTECTIVE ANTIGENS FROM HISTOPLASMA CAPSULATUM
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI034361-05 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Infection with the pathogenic fungus, Histoplasma capsulatum (Hc), produces a spectrum of illness ranging from acute pulmonary disease to chronic pulmonary infection to progressive disseminated histoplasmosis. In the vast majority of individuals, infection resolves without therapeutic intervention. Clearance of the organism is critically dependent on a collaboration between T cells and macrophages. It is presumed that upon recognition of antigen(s), Hc-reactive T cells release cytokines that activate macrophages to inhibit the intracellular growth of Hc. Two antigens, HIS-62 and HIS-80, have been shown to induce cellular immune responses in mice and mediate protection against Hc yeasts. Recently, the gene encoding HIS-62 has been cloned, sequenced and expressed and similar work on HIS-80 has begun. The overall objective of this proposal is to gain a better understanding of the interaction of T cells with Hc antigens. Since T cells ultimately respond to peptides, this proposal seeks to advance beyond the study of native HIS-62 and HIS- 80, and it will examine the immunobiological activity of peptides from these antigens. The specific aims are 1) To clone, sequence and express HIS-80. Recombinant proteins will be tested for their capacity to induce cellular immune responses in mice and to confer protection in models of pulmonary and systemic histoplasmosis; 2) To analyze the antigenicity and immunogenicity of peptides from HIS-62 and HIS-80, and 3) To generate murine T cell clones reactive with peptides. The clones will be analyzed for a) T cell receptor expression by molecular genetic techniques, b) proliferative responses to peptides c) cytokine production, d) ability to modify Hc infection, e) induction delayed-type hypersensitivity responses, and f) major histocompatibility complex restriction of recognition. Thus, it may be possible to correlate the functional activity of T cells with their expression of specific T cell receptor family. Furthermore, HIS-62 and HIS-80 may serve as a paradigm for the interaction of Hc antigens with T cells.
Keywords: Histoplasma capsulatum, cellular immunity, fungal antigen, histoplasmosis, microorganism immunology, T cell receptor, T lymphocyte, cytokine, delayed hypersensitivity, leukocyte activation /transformation, major histocompatibility complex, receptor expression, recombinant protein, Escherichia coli, clone cell, epitope mapping, laboratory mouse, molecular cloning, nucleic acid sequence
Project start date: 1993-07-01
Project end date: 1998-06-30
5R01AI034361-05 (1997): $239884
5R01AI034361-03 (1995): $225195
5R01AI034361-02 (1994): $227261
1R01AI034361-01 (1993): $220317
Sponsored Links Excellgen http://Excellgen.com
MOLECULAR AND CELL BIOLOGY OF FUNGAL PATHOGENS
George S Deepe, Professor
Internal Medicineuniversity Of Cincinnati
sponsored Research Services
cincinnati, Oh 45221
Grant 5P01AI028392-05 from National Institute Of Allergy And Infectious Diseases IRG: SRC
Abstract: In this program project we will conduct basic studies on medically important fungi at the molecular and cellular level to 1) enhance understanding of fungal pathogenesis; 2) develop biochemical markers of infection by fungi; 3) explore human phagocyte surface receptor interactions with ligands of Histoplasma capsulatum (Hc) and the subsequent signaling of intraphagocyte biochemical events; 4) further characterize the gene structure and organization of Pneumocystis carinii which we and others recently demonstrated to be a member of the fungi by small subunit ribosomal RNA comparative analysis. Proj. 1 will produce and characterize nucleic acid probes to analyze the gene(s) and other cognate proteins responsible for encoding a plasma membrane proton ion pump in Hc yeasts that maintains a reasonably constant internal pH and may enhance survival within the acidic milieu of host macrophage phagolysosomes. Proj. 2 will examine the fate of Histoplasma yeasts and microconidia in human monocyte/macrophages and alveolar macrophages. The ligands within yeasts and conidia that are recognized by the LFA-1,CR3,p150,95 receptors of macrophages will be identified and purified. Mechanisms of signal transduction initiated by yeast binding to these receptors will be compared to those induced by binding of C3bi-coated erythrocytes to CR3. Proj. 3 will study the role of elastinolytic proteinase in the virulence of invasive Aspergillus species by isolating and cloning the gene for Aspergillus elastase (AE). Cloned AE gene will be used to produce recombinant AE for use in diagnostic testing and virulence studies; the chromosomal location of the gene will be determined, and AE gene probes will be evaluated for diagnosis by in situ hybridization. Proj. 4 will pursue observations that pathogenic species of Aspergillus and Cryptococcus produce large amounts of the polyol, D-mannitol. Capillary gas-chromatography will be used to determine if this metabolite can be employed as a quantitative, diagnostic marker of invasive infection by these fungi in experimental animals and patients. Proj. 5 will extend our knowledge of the fungal nature of P. carinii by employing cloned DNA fragments to characterize gene structure and organization. Genes encoding ribosomal RNAs and the calmodulin gene will be primary cloning targets. Clones of rRNA genes, chromosome markers and repetitive elements will be used as hybridization probes to examine genomic variation among isolates of P. carinii from rat and human hosts
Keywords: Fungi, cellular, communicable disease diagnosis, immunodeficiency, molecular pathology, pathologic process recombinant protein
Project start date: 1990-01-01
Project end date: 1994-12-31
5P01AI028392-05 (1994): $695152
STUDIES OF H CAPSULATUM-REACTIVE MURINE T CELL CLONES
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI023017-08 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Human T-cell lines and clones that recognize Histoplasma capsulatum antigens will be developed to complement those isolated from mice. The surface phenotype, lymphokine production, response of cloned T cells to heterologous fungal antigens, and major histocompatibility complex restriction of proliferation, will be studied. Anti-idiotypic antibodies to human T-cell clones will be produced; using these antibodies, the surface receptor on T cells for Histoplasma antigens will be characterized biochemically. In parallel, Histoplasma yeast antigens from the cell wall/membrane that trigger proliferation by human and murine T-cell clones will be isolated and characterized. Yeasts will be disrupted and cell wall/membrane solubilized. this material will be subjected to SDS-PAGE and transferred to nitrocellulose. Stained bands will be cut, dissolved, and particle suspensions tested for immunoreactivity with T-cell clones. ONce the immunogenic fractions(s) has been identified, it will be purified by either preparative gel electrophoresis or gel chromatography followed by high performance liquid chromatography. The carbohydrate composition of the antigen will be analyzed by gas chromatography, and the nature of the antigen recognized by human and murine T cell clones will be determined by chemical and enzymatic degradative procedures. The gene encoding the protein portion of the H antigen will be cloned and inserted into an expression vector to produce a recombinant H antigen. The amino terminus of deglycosylated H will be amino acid sequenced. Oligonucleotide probes will be synthesized and used to screen by Southern blot analysis an established genomic library from strain G217B yeasts. Rapid sequencing of DNA will be performed. mRNA will be isolated and Northern blot analysis using nick-translated DNA performed to estimate message size. The sequence of genomic DNA will be analyzed for coding regions. The gene will be inserted into an expression vector and recombinant H antigen tested for immunoregulatory activity. These studies will identify purified yeast antigens recognized by T cells and provide a new approach (i.e., molecular cloning) for the isolation of H. capsulatum antigens. These antigens may be useful in the development of vaccines or as immunomodulatory agents for the treatment of histoplasmosis.
Keywords: Histoplasma capsulatum, T lymphocyte, clone cell, histoplasmosis, leukocyte activation /transformation, T cell receptor, antiidiotype antibody, chemical structure function, chimeric protein, fungal antigen, lymphokine, major histocompatibility complex, microorganism immunology, molecular cloning, nucleic acid probe, protein biosynthesis, SDS polyacrylamide gel electrophoresis, human genetic material tag, human subject, laboratory mouse, northern blotting, nucleic acid sequence, protein sequence, southern blotting, western blotting
Project start date: 1985-12-01
Project end date: 1994-06-30
5R01AI023017-08 (1993): $225572
H CAPSULATUM-REACTIVE MURINE T CELL CLONES
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI023017-07 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Human T-cell lines and clones that recognize Histoplasma capsulatum antigens will be developed to complement those isolated from mice. The surface phenotype, lymphokine production, response of cloned T cells to heterologous fungal antigens, and major histocompatibility complex restriction of proliferation, will be studied. Anti-idiotypic antibodies to human T-cell clones will be produced; using these antibodies, the surface receptor on T cells for Histoplasma antigens will be characterized biochemically. In parallel, Histoplasma yeast antigens from the cell wall/membrane that trigger proliferation by human and murine T-cell clones will be isolated and characterized. Yeasts will be disrupted and cell wall/membrane solubilized. this material will be subjected to SDS-PAGE and transferred to nitrocellulose. Stained bands will be cut, dissolved, and particle suspensions tested for immunoreactivity with T-cell clones. ONce the immunogenic fractions(s) has been identified, it will be purified by either preparative gel electrophoresis or gel chromatography followed by high performance liquid chromatography. The carbohydrate composition of the antigen will be analyzed by gas chromatography, and the nature of the antigen recognized by human and murine T cell clones will be determined by chemical and enzymatic degradative procedures. The gene encoding the protein portion of the H antigen will be cloned and inserted into an expression vector to produce a recombinant H antigen. The amino terminus of deglycosylated H will be amino acid sequenced. Oligonucleotide probes will be synthesized and used to screen by Southern blot analysis an established genomic library from strain G217B yeasts. Rapid sequencing of DNA will be performed. mRNA will be isolated and Northern blot analysis using nick-translated DNA performed to estimate message size. The sequence of genomic DNA will be analyzed for coding regions. The gene will be inserted into an expression vector and recombinant H antigen tested for immunoregulatory activity. These studies will identify purified yeast antigens recognized by T cells and provide a new approach (i.e., molecular cloning) for the isolation of H. capsulatum antigens. These antigens may be useful in the development of vaccines or as immunomodulatory agents for the treatment of histoplasmosis.
Keywords: Histoplasma capsulatum, T lymphocyte, clone cell, histoplasmosis, leukocyte activation /transformation, T cell receptor, antiidiotype antibody, chemical structure function, chimeric protein, fungal antigen, lymphokine, major histocompatibility complex, microorganism immunology, molecular cloning, nucleic acid probe, protein biosynthesis, SDS polyacrylamide gel electrophoresis, human clinical subject, human genetic material tag, laboratory mouse, northern blotting, nucleic acid sequencing, protein sequencing, southern blotting, western blotting
Project start date: 1985-12-01
Project end date: 1994-06-30
5R01AI023017-07 (1992): $239992
STUDIES OF H CAPSULATUM-REACTIVE MURINE T CELL CLONES
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI023017-06 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Human T-cell lines and clones that recognize Histoplasma capsulatum antigens will be developed to complement those isolated from mice. The surface phenotype, lymphokine production, response of cloned T cells to heterologous fungal antigens, and major histocompatibility complex restriction of proliferation, will be studied. Anti-idiotypic antibodies to human T-cell clones will be produced; using these antibodies, the surface receptor on T cells for Histoplasma antigens will be characterized biochemically. In parallel, Histoplasma yeast antigens from the cell wall/membrane that trigger proliferation by human and murine T-cell clones will be isolated and characterized. Yeasts will be disrupted and cell wall/membrane solubilized. this material will be subjected to SDS-PAGE and transferred to nitrocellulose. Stained bands will be cut, dissolved, and particle suspensions tested for immunoreactivity with T-cell clones. ONce the immunogenic fractions(s) has been identified, it will be purified by either preparative gel electrophoresis or gel chromatography followed by high performance liquid chromatography. The carbohydrate composition of the antigen will be analyzed by gas chromatography, and the nature of the antigen recognized by human and murine T cell clones will be determined by chemical and enzymatic degradative procedures. The gene encoding the protein portion of the H antigen will be cloned and inserted into an expression vector to produce a recombinant H antigen. The amino terminus of deglycosylated H will be amino acid sequenced. Oligonucleotide probes will be synthesized and used to screen by Southern blot analysis an established genomic library from strain G217B yeasts. Rapid sequencing of DNA will be performed. mRNA will be isolated and Northern blot analysis using nick-translated DNA performed to estimate message size. The sequence of genomic DNA will be analyzed for coding regions. The gene will be inserted into an expression vector and recombinant H antigen tested for immunoregulatory activity. These studies will identify purified yeast antigens recognized by T cells and provide a new approach (i.e., molecular cloning) for the isolation of H. capsulatum antigens. These antigens may be useful in the development of vaccines or as immunomodulatory agents for the treatment of histoplasmosis.
Keywords: Histoplasma capsulatum, T lymphocyte, clone cell, histoplasmosis, leukocyte activation /transformation, T cell receptor, antiidiotype antibody, chemical structure function, chimeric protein, fungal antigen, lymphokine, major histocompatibility complex, microorganism immunology, molecular cloning, nucleic acid probe, protein biosynthesis, SDS polyacrylamide gel electrophoresis, human clinical subject, human genetic material tag, immunoblotting, laboratory mouse, northern blotting, nucleic acid sequencing, protein sequencing, southern blotting
Project start date: 1985-12-01
Project end date: 1994-06-30
H CAPSULATUM-REACTIVE T CELL CLONES
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI023017-10 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Histoplasma capsulatum is a dimorphic, pathogenic fungus that produces a wide spectrum of illness ranging from a mild, acute pulmonary infection to a life- threatening progressive, disseminated disease. Successful resolution of infection requires an interaction between T cells and macrophages. Although the latter are the principal habitat and primary effector cells, T cells play a vital and essential role in host resistance to this fungus. We have demonstrated that, in mice, in vivo depletion of either CD4+ or CD8+ T cells is associated with increased severity of infection. Elimination of CD4+ T cells results in death of mice challenged with a sublethal inoculum. Depletion of CD8+ T cells impairs the efficiency of clearance of H. capsulatum from viscera. Thus, optimal clearance of infection requires both T cell subsets. Prior studies with intracellular non-viral pathogens suggest that cytotoxic CD4+ or CD8+ play an important role in recovery from infection. In this proposal, we will test the hypothesis that cytotoxic CD4+ and CD8+ T cells contribute to host defenses against this fungus. The specific objectives of this grant are to l) Examine the in vitro immunobiological activity of murine H. capsulatum-reactive cytotoxic CD4+ and CD8+ T cells. Specifically, T cell clones will be generated and tested for their capacity to lyse yeast- infected macrophages. Moreover, we will determine the fate of H. capsulatum yeasts in macrophages exposed to cytotoxic T cells, and map the antigens recognized by cytotoxic T cells; 2) Analyze the in vivo functional activity of murine cytotoxic T cell clones. T cell clones will be tested for their capacity to confer protection against a challenge with H. capsulatum, and 3) Determine if human H. capsulatum-reactive CD4+ and CD8+ T cells express cytotoxic activity. Human T cell clones will be analyzed for their ability to lyse yeast-infected human macrophages. Subsequently, we will determine if human cytotoxic T cells alter the fate of yeast cells in human macrophages. These studies will provide further insight into the mechanisms of T cell-mediated immunity.
Keywords: Histoplasma capsulatum, T lymphocyte, cellular immunity, clone cell, histoplasmosis, antigen presentation, cytotoxic T lymphocyte, fungal antigen, helper T lymphocyte, macrophage, monoclonal antibody, polymerase chain reaction, protein sequence, western blotting
Project start date: 1985-12-01
Project end date: 1997-06-30
5R01AI023017-10 (1995): $188819
2R01AI023017-09 (1994): $178223
PROTECTIVE ANTIGENS FROM HISTOPLASMA CAPSULATUM
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI034361-10 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Adapted from applicants ) Protective immunity to the pathogenic fungus, Histoplasma capsulatum (Hc) requires an interaction between macrophages and T cells. The latter play a pivotal role in host resistance by releasing cytokines that arm macrophages to express antifungal activity. For T cells to become activated they must recognize peptide epitopes from antigen that have been degraded by macrophages. The Histoplasma antigen HSP 60 antigens induces a cellular immune response that confers protective immunity. Two others, HSP 70 and H antigen, trigger a cellular immune response, but fail to mediate a protective immune response. These results indicate that not all antigens may stimulate protective cellular activity. The reasons for this disparity in biological activities between protective and non-protective Histoplasma antigens is not known, but this information is critically important for understanding the basis for vaccine-associated immunity. This proposal will test the hypothesis that the difference between a protective and a non-protective Histoplasma antigen is determined by the profile of cytokines generated in response to vaccination, the T cell repertoire induced by vaccination, the induction of co-stimulatory molecules on antigen-presenting cells or a combination of these processes. Specific Aim 1 will endeavor to determine if the host response to hsp 60 differs from that of hsp 70. The following will be analyzed i) cytokine production in lymphoid tissue; ii) inflammation to each antigen; and iii) expression of CD80 and CD86. Specific Aim 2 will determine the functional importance of cytokines, T cells and co-stimulatory molecules and protective efficacy. The emphasis will be in determining which cytokines may be critical for hsp 60-induced immunity, the T cell populations that are necessary for the efficacy of hsp 60, the role of CD80 and CD86, and the whether the immunogenicity of rhsp 70 can be enhanced. Although hsp 60 may be protective, this proposal seeks to identify other protective antigens. In Specific Aim 3 a new strategy will be pursued to identify new antigens that could elicit protective immunity. This strategy is based on the hypothesis that Histoplasma peptides derived from the processing of viable yeast antigens and bound to class II major histocompatibility complex (MHC) molecules are central determinants of CD4+ T cell activation. Aim 3 will identify naturally processed peptides on class II MHC to determine their amino acid sequence, clone and express the genes encoding the peptides, and determine if they stimulate the inductive phase of T cell-mediated immune responses to Histoplasma.
Keywords: Histoplasma capsulatum, antigen presentation, cellular immunity, cytokine, fungal antigen, host organism interaction, microorganism immunology, MHC class II antigen, T lymphocyte, gene expression, histoplasmosis, leukocyte activation /transformation, macrophage, peptide, recombinant protein, flow cytometry, laboratory mouse, molecular cloning, neutralizing antibody, protein sequence, southern blotting
Project start date: 1993-07-01
Project end date: 2003-06-30
5R01AI034361-10 (2002): $289202
5R01AI034361-09 (2001): $280779
5R01AI034361-08 (2000): $272602
Sponsored Links Excellgen http://Excellgen.com
5R01AI034361-07 (1999): $273841
2R01AI034361-06 (1998): $256953
T CELL RECEPTOR USAGE IN PULMONARY HISTOPLASMOSIS
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 1R37AI042747-01 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Adapted from s ) Infection with the pathogenic fungus, Histoplasma capsulatum (Hc) is initiated by coincidental inhalation of conidia and hyphal fragments. In lungs, these elements convert into yeast cells which are the form that is responsible for the clinicopathological manifestations of disease. Successful resolution of infection requires a collaborative interaction between T cells and macrophages. The principal mechanism whereby T cells contribute to effective clearance of the fungus is by release of cytokines that arm macrophages to inhibit the intracellular growth of yeast cells. Although several lines of evidence support the integral role of T cells in host resistance, much of the work has analyzed polyclonal T cells from lymphoid organs. In this proposal, Dr. Deepe will examine the T cell receptor (TCR) repertoire in lungs of naive and immune mice exposed to Hc. The hypothesis is that there is a bias in the TCR repertoire in the lungs of mice and that the overrepresented cells are key to host defenses. Preliminary data indicate that in naive mice there is a bias in the TCR repertoire during the first 21 days of infection. In Specific Aim 1) the investigator will analyze the VB repertoire in immune mice reexposed to Hc using reverse transcription-polymerase chain reaction combined with Southern hybridization and the results confirmed with flow cytometry; 2) determine if the V beta repertoire varies among Hc isolates; 3) determine if the anatomic location of prominent V beta cells in inflamed lungs differs from the other V beta bearing T cells, and 4) determine if the overexpressed V beta cells are of clonal origin. In Specific Aim 2, the investigator will analyze the functional properties of overexpressed V beta cells. Dr. Deepe will 1) determine if the course of pulmonary Hc or the inflammatory response to Hc is altered by elimination of one or more T cell populations bearing the most prominent V beta families; 2) determine if passive transfer of prominent V beta bearing T cell clones alters the course of pulmonary Hc and 3) determine if the prominent V beta cells are the principal generators of lymphokines involved in protection in Specific Aim 3, the investigator will determine the immunobiological importance of antigens that stimulate overexpressed V beta . Dr. Deepe will 1) identify antigens that are recognized by the prominent V beta using an epitope-tagged cDNA library, and 2) determine if deletion of the gene encoding the antigen(s) causes deviation of the immune response to Hc. Hence, there will be an understanding at the clonal level the critical function(s) of these T cells.
Keywords: T cell receptor, cellular immunity, histoplasmosis, lung disorder, T lymphocyte, cell population study, disease model, fungal antigen, host organism interaction, immunoglobulin isotype, inflammation, lymphokine, macrophage, Histoplasma capsulatum, clone cell, flow cytometry, genetic library, laboratory mouse, polymerase chain reaction, southern blotting, yeast
Project start date: 1997-07-15
Project end date: 2002-06-30
1R37AI042747-01 (1997): $196165
5R37AI042747-05 (2001): $258604
5R37AI042747-04 (2000): $264571
5R37AI042747-03 (1999): $199517
5R37AI042747-02 (1998): $193707
George S Deepe
University Of Cincinnati
Project start date: 2010-02-01
Project end date: 2015-01-31
Protective Antigens From Histoplasma Capsulatum
George S Deepe, Professor
Internal Medicineuniversity Of Cincinnati
sponsored Research Services
cincinnati, Oh 45221
Grant 5R01AI034361-15 from National Institute Of Allergy And Infectious Diseases IRG: BM
Keywords: Histoplasma, antigen, cell Fungi, T cell receptor, acid, active immunization, antigen presenting cell, arm, base, bias, birth, bovine serum albumin, cell wall, colony stimulating factor, cytokine, dendritic cell, element, evolution, family, granulocyte, heat, heat shock protein, histoplasmosis, immunity, immunization, infection, insight, interferon, interleukin 10, interleukin 12, interleukin 4, intracellular, lipid, macrophage, major histocompatibility complex, memory, model, monoclonal antibody, motivation, necrosis, neoplasm /cancer, oligopeptide, peptide, phagocyte, phenotype, polymerase chain reaction, protein, role, shock, vaccine
Project start date: 1993-07-01
Project end date: 2008-12-31
5R01AI034361-15 (2007): $347259
Sponsored Links Excellgen http://Excellgen.com
5R01AI034361-14 (2006): $358213
T Cell Receptor Usage In Pulmonary Histoplasmosis
George S Deepe, Professor
Internal Medicineuniversity Of Cincinnati
sponsored Research Services
cincinnati, Oh 45221
Grant 5R37AI042747-10 from National Institute Of Allergy And Infectious Diseases IRG: NSS
Keywords: T cell receptor, cellular immunity, histoplasmosis, lung disorder T lymphocyte, cell population study, disease /disorder model, fungal antigen, host organism interaction, immunoglobulin isotype, inflammation, lymphokine, macrophage Histoplasma, clone cell, flow cytometry, genetic library, laboratory mouse, polymerase chain reaction, southern blotting, yeast
Project start date: 1997-07-15
Project end date: 2008-06-30
5R37AI042747-10 (2006): $325482
Protective Antigens From Histoplasma Capsulatum
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI034361-13 from National Institute Of Allergy And Infectious Diseases IRG: BM
Project start date: 1993-07-01
Project end date: 2007-12-31
5R01AI034361-13 (2005): $367407
T Cell Receptor Usage In Pulmonary Histoplasmosis
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R37AI042747-09 from National Institute Of Allergy And Infectious Diseases IRG: NSS
Keywords: T cell receptor, cellular immunity, histoplasmosis, lung disorder, T lymphocyte, cell population study, disease /disorder model, fungal antigen, host organism interaction, immunoglobulin isotype, inflammation, lymphokine, macrophage, Histoplasma, clone cell, flow cytometry, genetic library, laboratory mouse, polymerase chain reaction, southern blotting, yeast
Project start date: 1997-07-15
Project end date: 2007-06-30
5R37AI042747-09 (2005): $335251
Protective Antigens From Histoplasma Capsulatum
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI034361-12 from National Institute Of Allergy And Infectious Diseases IRG: BM
Project start date: 1993-07-01
Project end date: 2007-12-31
5R01AI034361-12 (2004): $375601
T Cell Receptor Usage In Pulmonary Histoplasmosis
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R37AI042747-08 from National Institute Of Allergy And Infectious Diseases IRG: NSS
Keywords: T cell receptor, cellular immunity, histoplasmosis, lung disorder, T lymphocyte, cell population study, disease /disorder model, fungal antigen, host organism interaction, immunoglobulin isotype, inflammation, lymphokine, macrophage, Histoplasma, Histoplasma capsulatum, clone cell, flow cytometry, genetic library, laboratory mouse, polymerase chain reaction, southern blotting, yeast
Project start date: 1997-07-15
Project end date: 2007-06-30
5R37AI042747-08 (2004): $337110
5R37AI042747-07 (2003): $338897
4R37AI042747-06 (2002): $353863
H CAPSULATUM-REACTIVE T CELL CLONES
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI023017-11 from National Institute Of Allergy And Infectious Diseases IRG: BM
Project start date: 1985-12-01
Project end date: 1997-06-30
5R01AI023017-11 (1996): $193969
PROTECTIVE ANTIGENS FROM HISTOPLASMA CAPSULATUM
George S Deepe, Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 5R01AI034361-04 from National Institute Of Allergy And Infectious Diseases IRG: BM
Project start date: 1993-07-01
Project end date: 1998-06-30
5R01AI034361-04 (1996): $233109
Sponsored Links Excellgen http://Excellgen.com