GAMMA-INTERFERON GENE-EXPRESSION AND RELEASE IN HUMAN-LYMPHOCYTES DIRECTLY ACTIVATED BY CRYPTOCOCCUS-NEOFORMANS AND CANDIDA-ALBICANS

Previous studies in our laboratory and others have demonstrated that T and/or NK cells can directly bind to and inhibit the growth of the me dically important fungal pathogens Cryptococcus neoformans and Candida albicans by apparently non-major histocompatibility complex-restricte d mechanisms. Here, we examined whether this direct interaction betwee n lymphocytes and fungi also results in cytokine gene expression and r elease. Nonadherent lymphocytes (NAL), isolated from human peripheral blood mononuclear cells by depletion of cells adherent to plastic and nylon wool, released gamma interferon (IFN-gamma), but not interleukin -4 (IL-4) and IL-10, following stimulation with C. neoformans yeast ce lls and C. albicans yeast cells, hyphae, and supernatants. The fungal stimuli also induced IFN-gamma mRNA, with peak gene expression seen at or after 18 h. IFN-gamma release was still seen even when either NK c ells or T lymphocytes were depleted by negative selection, suggesting that both cell types can be stimulated by fungi to produce IFN-gamma. Release of IFN-gamma from fungus-stimulated NAL occurred in the absenc e of an intact complement system and was not especially enhanced by cu lture with IL-2 or IL-12. These data expand the mechanisms by which th e direct interaction of NAL with fungal targets can lead to immune act ivation. Moreover, to our knowledge, this is the first demonstration o f direct stimulation of T-cell cytokine release by microbial pathogens .