AbstractIt has recently been established that FcRs are involved in the triggering of type II and III inflammatory responses. Although FcR is not believed to be involved in the regulation of T cell function, the in vivo contribution of FcRs to T cell function still remains unclear. We analyzed in vivo responses of delayed-type hypersensitivity and proliferation of CD4+ T cells to Ags in FcRγ−/− mice lacking the expression and function of FcγRI, FcγRIII, and FcεRI. We found that the delayed-type hypersensitivity response in FcRγ−/− mice is significantly decreased compared with that in wild-type mice. Moreover, the secondary responses of proliferation and cytokine production as well as the Ab formation by CD4+ T cells from FcRγ−/− mice to Ag and normal APCs were also reduced. In contrast, in vitro primary T cell proliferative responses upon stimulation with anti-TCR Ab or MLR as well as in vivo primary response against staphylococcus enterotoxin B administration were not different between T cells from FcRγ−/− and wild-type mice. In addition, the Ag presentation function of APCs from unimmunized FcRγ−/− mice was normal. On the other hand, Ab-deficient mice also revealed impaired T cell responses. These results demonstrate that the defective T cell responses in FcRγ−/− mice were due to impaired Ag presentation during in vivo priming not to a defect in T cells. Therefore, they suggest that the FcRs on APCs mediate efficient priming of Th cell responses in vivo in an immune complex-dependent manner.