The modulation of B7.2 and B7.1 on B cells by immunosuppressive agents

Several recent studies demonstrate that B7.2, but not B7.1, play an importa nt role in allergic inflammation and IgE production. Agents that down-regul ate B7.2 may therefore be of benefit for the treatment of Th2-driven allerg ic diseases. Our current study was carried our to investigate the effect of immunosuppressive agents, cyclosporin A (CsA) and dexamethasone, on B7.2 a nd B7.1 expression on B cells stimulated with the superantigen, toxic shock syndrome toxin-1 (TSST-1). The analysis of B7.2 and B7.1 on the same cells by flow cytometry demonstrated that TSST-1 up-regulated B7.2(+)B7.1(-) but not B7.1(+)B7.2(-) on B cells in a dose-dependent fashion. CsA and dexamet hasone significantly downregulated B7.2(+)B7.1(-) but up-regulated B7.2(-)B 7.1(+) B cells in the presence or absence of TSST-1 (100 ng/ml). Interestin gly, the combination of CsA and dexamethasone was much more potent in the i nhibition of B7.2 expression than either of these agents alone. As CD40 is known to up-regulate B7.2 expression on B cells, the mechanism of B7.2 down -regulation by CsA and dexamethasone was further studied by investigating t he effect of these agents on CD40 expression on B cells. TSST-1 significant ly increased CD40 expression on B cells. However, the addition of CsA or de xamethasone significantly down-regulated CD40 expression. Anti-CD40 MoAb si gnificantly reversed the effects of CsA or dexamethasone on B7.2 and B7.1 e xpression, suggesting that T cell engagement of CD40 plays a role in the me chanisms by which CsA and dexamethasone acts on B cells. These data demonst rate the modulatory effect of CsA and dexamethasone on B7.2 and B7.1 expres sion on B cells and the potential role of CD40 in mediating this effect.