IN-VIVO DEPLETION OF MURINE CD8 POSITIVE T-CELLS IMPAIRS SURVIVAL DURING INFECTION WITH A HIGHLY VIRULENT-STRAIN OF CRYPTOCOCCUS-NEOFORMANS

Cell-mediated immunity plays an important but incompletely understood role in host defense against Cryptococcus neoformans. Because of their multiple capacities as cytokine-secreting cells, cytotoxic cells, and antigen-specific suppressor cells, CD8 positive T lymphocytes could p otentially either enhance or impair host defense against C. neoformans . To determine whether CD8 T cells enhance or inhibit host defence dur ing an infection with a highly virulent strain of C. neoformans, we ex amined the effect of in vivo CD8 cell depletion on survival and on the number of organisms in mice infected by either the intratracheal or i ntravenous routes. Adequacy of depletion was confirmed both phenotypic ally and functionally. Regardless of the route of infection, we found that survival of mice depleted of CD8 T cells was significantly reduce d compared to undepleted mice. Surprisingly, however, CD8 depletion di d not alter organism burden measured by quantitative CFU assay in mice infected by either route. These data demonstrate that CD8 positive T cells participate in the immune response to a highly virulent strain o f C. neoformans. By contrast to minimally virulent isolates that do no t cause a life threatening infection, the immune response to a highly virulent isolate does not alter the burden of organisms, but does enha nce host defense as it is necessary for the optimal survival of infect ed mice.