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Since cell-mediated immunity (CMI) is critical for host defenses against the encapsulated fungus Cryptococcus neoformans, the production of human antifungal effector cells as a consequence of the CMI response was investigated. Peripheral blood mononuclear cells (PBMC) were stimulated in culture with killed C. neoformans. Stimulated (but not unstimulated) PBMC killed a subsequent inoculum of live encapsulated organisms, with maximal killing seen after 3-7 days. Killing required the presence of both adherent and nonadherent stimulated PBMC and was enhanced by anticapsular antibody. In contrast, unstimulated PBMC and the adherent fraction of stimulated PBMC killed an isogenic acapsular strain of C. neoformans. These data suggest that the CMI response controls cryptococcosis by eliciting two populations of fungicidal cells acting synergistically. Moreover, capsule, by thwarting the ability of unstimulated PBMC to kill C. neoformans, seems to obligate the host to mount an immune response to generate fungicidal cells.
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