CRYPTOCOCCUS-NEOFORMANS DIFFERENTLY REGULATES B7-1 (CD80) AND B7-2 (CD86) EXPRESSION ON HUMAN MONOCYTES

To induce a specific response in primary resting T cells, two signals must be provided by antigen-presenting cells (APC). The first antigen- specific signal is mediated by formation of ii the T cell receptor maj or histocompatibility complex molecule ternary complexes. The second s ignal is delivered by interaction of either B7-1 or B7-2 expressed by APC with CD28 or CTLA-4 on T cells. In this study, we examined the mod ulation of B7-1 and B7-2 molecules on human monocytes exposed to encap sulated or acapsular Cryptococcus neoformans or Candida albicans. In o ur experimental system, C. albicans or acapsular C. neoformans are abl e to induce B7-1 expression while the encapsulated yeast is a poor sti mulator. A modest increase of B7-2 expression was also observed after monocyte treatment with acapsular C. neoformans or C. albicans, while the encapsulated yeast was ineffective in inducing B7-2 molecules. Kin etic analysis showed the maximum expression of B7-1 after 24 to 48 h. Addition of the opsonic IgG1 mAb 2H1 to monocytes and C. neoformans si gnificantly increased B7-1, but not B7-2, expression. The contribution of B7-1 and B7-2 cc-stimulatory (CS) molecules to cryptococcal-specif ic T cell activation was analyzed and a substantial inhibition of T ce ll proliferation was observed. In this study we provide the first demo nstration of fungal interference in the regulation of CS molecules. Ou r results suggest a potential mechanism for poor inflammatory response s observed in C. neoformans infections.