CD4+CD25+ regulatory T cells control the magnitude of T-dependent humoral immune responses to exogenous antigens

CD4(+)CD25(+) T reg cells are critical for peripheral tolerance and prevention of autoimmunity. Here we show that CD4(+)CD25(+) T reg also regulate the magnitude of humoral responses against a panel of T-dependent antigens of foreign origin during both primary and secondary immune responses. Depletion of CD4(+)CD25(+) T cells leads to increased antigen-specific antibody production and affinity maturation but does not affect T-independent B cell responses, suggesting that CD4(+)CD25(+) T reg exert a feedback mechanism on non-self antigen-specific antibody secretion by dampening the T cell help for B cell activation. Moreover, we show that CD4(+)CD25(+) T reg also suppress in vitro B cell immunoglobulin production by inhibiting CD4(+)CD25(-) T cell help delivery, and that blockade of TGF-beta activity abolishes this suppression.