Fcγ receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses

The uptake of immune complexes by FcRs on APCs augments humoral and cellular responses to exogenous Ag. In this study, CD11c(+) dendritic cells are shown to be responsible in vivo for immune complex-triggered priming of T cells. We examine the consequence of Ab-mediated uptake of self Ag by dendritic cells in the rat insulin promoter-membrane OVA model and identify a role for the inhibitory Fc gamma RIIB in the maintenance of peripheral CD8 T cell tolerance. Effector differentiation of diabetogenic OT-I CD8(+) T cells is enhanced in rat insulin promoter-membrane OVA mice lacking Fc gamma RIIB, resulting in a high incidence of diabetes. Fc gamma RIIB-mediated inhibition of CD8 T cell priming results from suppression of both DC activation and cross-presentation through activating Fc gamma Rs. Further Fc gamma RIIB on DCs inhibited the induction of OVA-specific Th1 effectors, limiting Th1-type differentiation and memory T cell accumulation. In these MHC II-restricted responses, the presence of Fc gamma RIIB only modestly affected initial CD4 T cell proliferative responses, suggesting that Fc gamma RIIB limited effector cell differentiation primarily by inhibiting DC activation. Thus, Fc gamma RIIB can contribute to peripheral tolerance maintenance by inhibiting DC activation alone or by also limiting processing of exogenously acquired Ag.