ANTIGEN-INDUCED PROTECTIVE AND NONPROTECTIVE CELL-MEDIATED IMMUNE COMPONENTS AGAINST CRYPTOCOCCUS-NEOFORMANS

Mice immunized with two different cryptococcal antigen preparations, o ne a soluble culture filtrate antigen (CneF) in complete Freund's adju vant (CFA) and the other heat-killed Cryptococcus neoformans cells (HK C), develop two different profiles of activated T cells. CneF-CFA indu ces CD4(+) T cells responsible for delayed-type hypersensitivity (DTH) reactivity and for amplification of the anticryptococcal DTH response , whereas HKC induce CD4(+) and CD8(+) T cells involved in anticryptoc occal DTH reactivity and activated T cells which directly kill C. neof ormans cells. The main purpose of this study was to assess the level o f protection afforded by each of the two different T-cell profiles aga inst challenge with viable C. neoformans cells, thereby identifying wh ich activated T-cell profile provides better protection. CBA/J mice im munized with CneF-CFA had significantly better protective responses, b ased on better clearance of C. neoformans from tissues, on longer surv ival times, and on fewer and smaller lesions in the brain, than HKC-im munized mice or control mice similarly infected with C. neoformans. Bo th immunization protocols induced an anticryptococcal DTH response, bu t neither induced serum antibodies to glucuronoxylmannan, so the prote ction observed in the CneF-CFA immunized mice was due to the activated T-cell profile induced by that protocol. HKC-immunized mice, which di splayed no greater protection than controls, did not have the amplifie r cells. Based on our findings, we propose that the protective anticry ptococcal T cells are the CD4(+) T cells which have been shown to be r esponsible for DTH reactivity and/or the CD4(+) T cells which amplify the DTH response and which have been previously shown to produce high levels of gamma interferon and interleukin 2. Our results imply that t here are protective and nonprotective cell-mediated immune responses a nd highlight the complexity of the immune response to C. neoformans an tigens.