Protective Immunity against Experimental Pulmonary Cryptococcosis in T Cell-Depleted Mice

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 II99 gamma, 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 H99 gamma 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 H99 gamma 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 naive mice. Lastly, immunization of immunocompetent mice with C. neoformans strain H99 gamma 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.