DEPLETION OF MURINE CD8-CELLS INVIVO DECREASES PULMONARY CLEARANCE OFA MODERATELY VIRULENT-STRAIN OF CRYPTOCOCCUS-NEOFORMANS( T)

Host defense mechanisms to the important fungal pathogen Cryptococcus neoformans are complex and incompletely understood. From in vitro stud ies, we could expect CD8+ T cells to have the potential for both prote ctive and suppressive effects on defense against cryptococci. The curr ent study used the technique of in vivo subset depletion to determine the net effect of CD8+ T cells during actual infection. Mice depleted of CD8+ T cells by monoclonal antibody (YTS 169.4) injections were inf ected with the moderately virulent cryptococcal strain 613D by the int ratracheal route, which mimics natural pulmonary infection. To ensure adequacy of depletion, T cell subsets were enumerated by flow cytometr y in blood, spleen, lymph node, and lung. Specific elements of host de fense were measured by clearance of cryptococci in vivo and by the res ponse to cryptococcal antigens, both in vivo by delayed-type hypersens itivity (DTH) and in vitro by lymphocyte proliferation. We found that depletion of CD8+ 7 cells decreased pulmonary clearance of C. neoforma ns. CD8 depletion abrogated DTH without affecting antigen recognition or lymphocyte proliferation in vitro. These data demonstrate that the not effect of CD8+ T cells to a moderately virulent strain of C. neofo rmans is to enhance rather than suppresses host defenses. Abrogation o f DTH suggests that CD8+ T cells contribute to the protective immunolo gic response to C. neoformans. It is possible that in hosts deficient in CD4 cells, such as patients with AIDS, the protective effects of CD 8+ T cells could be stimulated by selected immunizing epitopes.