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 the T cell receptor major histocompatibility complex molecule ternary complexes. The second signal 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 modulation of B7‐1 and B7‐2 molecules on human monocytes exposed to encapsulated or acapsular Cryptococcus neoformans or Candida albicans. In our experimental system, C. albicans or acapsular C. neoformans are able to induce B7‐1 expression while the encapsulated yeast is a poor stimulator. 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. Kinetic 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 significantly increased B7‐1, but not B7‐2, expression. The contribution of B7‐1 and B7‐2 co‐stimulatory (CS) molecules to cryptococcal‐specific T cell activation was analyzed and a substantial inhibition of T cell proliferation was observed. In this study we provide the first demonstration of fungal interference in the regulation of CS molecules. Our results suggest a potential mechanism for poor inflammatory responses observed in C. neoformans infections.