title: Protective immunity against experimental pulmonary cryptococcosis in T cell-depleted mice.
abstract: Individuals with defects in T cell-mediated immunity (CMI) are highly susceptible to infection with Cryptococcus neoformans. The purpose of these studies was to determine if protection against experimental pulmonary cryptococcosis can be generated in T cell-deficient hosts. BALB/c mice were depleted of CD4⁺and/or CD8⁺ T cells or given an isotype control antibody prior to vaccination with a C. neoformans strain, designated H99γ, previously shown to induce protection against C. neoformans infection in immunocompetent mice. Mice depleted of CD4⁺ or CD8⁺ T cells, but not both subsets, survived an acute pulmonary infection with C. neoformans strain H99γ and a subsequent second challenge with wild-type C. neoformans strain H99. We observed a significant increase in the percentage of CD4⁺ and CD8⁺ T cells expressing the activation marker CD69 in the lungs of mice immunized with C. neoformans strain H99γ prior to a secondary challenge with wild-type cryptococci. CD4⁺ T cells within the lungs of immunized mice also appeared to acquire a predominantly activated effector memory cell phenotype (CD69⁺ CD44⁺ CCR7⁻ CD45RB⁻ CD62L⁻) following a second pulmonary challenge with wild-type C. neoformans, compared to CD4⁺ T cells from naïve mice. Lastly, immunization of immunocompetent mice with C. neoformans strain H99γ prior to depletion of CD4⁺ and/or CD8⁺ T cells resulted in significant protection against a second challenge with wild-type C. neoformans. Our studies demonstrate that protective immunity against pulmonary cryptococcosis can be generated in immunosuppressed hosts, thus supporting the development of cryptococcal vaccines.
authors: Department Biology, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-0062, USA.
authors: Karen L
authors: KL
authors: Wozniak
authors: Mattie L
authors: ML
authors: Young
authors: Floyd L
authors: FL
authors: Wormley
mesh_terms: D000818:Animals; D003453:Cryptococcosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D003455:Cryptococcus neoformans / Q000276:immunology*; D005260:Female; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*