CD8 CELLS PLAY A CRITICAL ROLE IN DELAYED-TYPE HYPERSENSITIVITY TO INTACT CRYPTOCOCCUS-NEOFORMANS

Although cell-mediated immunity is critical for optimal host defense t o C. neoformans, the role of T lymphocyte subsets is complex and poorl y understood. CD8 cells are important both for optimal host defense ag ainst C. neoformans, and for expression of delayed type hypersensitivi ty (DTH). Because host defense correlates with the ability to mount a DTH response to C. neoformans, the current studies were performed to d etermine the mechanism by which CD8 cells participate in DTH. Mice wer e immunized by the intratracheal route with live C. neoformans, or by the subcutaneous route with heat-killed C. neoformans. Mice were deple ted of CD8 cells in vivo by administration of mAb. After challenge wit h soluble cryptococcal Ag, the DTH response was quantified as footpad swelling. We found that mice depleted of CD8 cells before immunization were unable to express DTH. Mice depleted of CD8 cells after immuniza tion but before challenge also were unable to express DTH. Splenocytes of mice depleted of CD8 cells in vivo, before immunization, failed to transfer DTH to naive, undepleted mice. Immune splenocytes depleted o f CD8 cells in vitro also failed to transfer DTH to naive, undepleted mice. These data indicate that CD8 cells were necessary during the cha llenge and immunizing phases of DTH, and were necessary for expression of DTH. However, CD8 cell depletion did not abrogate DTH in mice immu nized with either soluble cryptococcal Ag in complete Freund's adjuvan t, or sheep red blood cells, which are mediated by CD4 cells. These da ta suggest that CD8 cells play a critical role in the cell-mediated im mune response to C. neoformans. Based on this information, it may be p ossible to protect hosts with deficiencies of CD4 cells, such as in AI DS, by designing immunizing strategies for stimulating CD8 cells.