LYMPHOPROLIFERATION AND CYTOKINE PROFILES IN HUMAN PERIPHERAL BLEED MONONUCLEAR-CELLS STIMULATED BY CRYPTOCOCCUS-NEOFORMANS

Cell-mediated immunity is critical to host defenses against the fungal infection cryptococcosis. Here, two functions critical to effective c ell-mediated immunity (CMI), lymphoproliferation and cytokine release, were studied in Cryptococcus neoformans-stimulated peripheral blood m ononuclear cells (PBMC) from seven healthy donors (controls) and two p atients with cryptococcosis. PBMC responses to C. neoformans were comp ared with responses to Candida albicans. Control and patient PBMC had significant lymphoproliferation in response to whole C. neoformans, wi th peak proliferation seen following 8 days of culture, but only patie nt PBMC proliferated when stimulated with C. neoformans mannoprotein. C. neaformans-stimulated control PBMC released IL-2, IFN-gamma, and IL -10 into the supernatant with peak or near peak concentrations of thes e three cytokines generally seen by day 1. Release of IL-4 was low or undetectable. In contrast, C. neoformans-stimulated patient PBMC relea sed IFN-gamma, which peaked on day 7, as well as IL-4, IL-10, and in o ne of two patients, IL-2. Cytokine release occurred later in patient ( compared with control) PBMC. Lymphoproliferation and cytokine release were similar comparing control PBMC stimulated with C. neoformans vers us Candida albicans. Thus, the magnitude and kinetics of the lymphopro liferative response to whole C. neoformans is similar comparing PBMC f rom controls and patients, but the cytokine profiles differ. Moreover, the capacity of patient PBMC to respond to soluble mannoprotein lends support to studies of mannoprotein components as vaccine candidates.