title: Diversity of the T-cell response to pulmonary Cryptococcus neoformans infection.
abstract: Cell-mediated immunity plays an important role in immunity to the pathogenic fungus Cryptococcus neoformans. However, the antigen specificity of the T-cell response to C. neoformans remains largely unknown. In this study, we used two approaches to determine the antigen specificity of the T-cell response to C. neoformans. We report here that a diverse T-cell receptor (TCR) Vbeta repertoire was maintained throughout the primary response to pulmonary C. neoformans infection in immunocompetent mice. CD4+ T-cell deficiency resulted in relative expansion of all CD8+ T-cell subsets. During a secondary immune response, preferential usage of a TCR Vbeta subset in CD4+ T cells occurred in single individuals, but the preferences were "private" and not shared between individuals. Both CD4+ and CD8+ T cells from the secondary lymphoid tissues of immunized mice proliferated in response to a variety of C. neoformans antigens, including heat-killed whole C. neoformans, culture filtrate antigen, C. neoformans lysate, and purified cryptococcal mannoprotein. CD4+ and CD8+ T cells from the secondary lymphoid tissues of mice undergoing a primary response to C. neoformans proliferated in response to C. neoformans lysate. In response to stimulation with C. neoformans lysate, lung CD4+ and CD8+ T cells produced the effector cytokines tumor necrosis factor alpha and gamma interferon. These results demonstrate that a diverse T-cell response is generated in response to pulmonary C. neoformans infection.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 6301 MSRB III, University of Michigan, Ann Arbor, Michigan 48109-0642, USA.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Lindell
authors.forename: Megan N
authors.initials: MN
authors.lastname: Ballinger
authors.forename: Roderick A
authors.initials: RA
authors.lastname: McDonald
authors.forename: Galen B
authors.initials: GB
authors.lastname: Toews
authors.forename: Gary B
authors.initials: GB
authors.lastname: Huffnagle
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma