FcR? controls the fas-dependent regulatory function of lymphoproliferative double negative T cells.

ABSTRACT: Patients with autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferation (LPR) mice are deficient in Fas, and accumulate large numbers of ??-TCR(+), CD4(-), CD8(-) double negative (DN) T cells. The function of these DN T cells remains largely unknown. The common ? subunit of the activating Fc receptors, FcR?, plays an important role in mediating innate immune responses. We have shown previously that a significant proportion of DN T cells express FcR?, and that this molecule is required for TCR transgenic DN T cells to suppress allogeneic immune responses. Whether FcR? plays a critical role in LPR DN T cell-mediated suppression of immune responses to auto and allo-antigens is not known. Here, we demonstrated that FcR?(+), but not FcR?(-) LPR DN T cells could suppress Fas(+) CD4(+) and CD8(+) T cell proliferation in vitro and attenuated CD4(+) T cell-mediated graft-versus host disease. Although FcR? expression did not allow LPR DN T cells to inhibit the expansion of Fas-deficient cells within the LPR context, adoptive transfer of FcR?(+), but not FcR?(-), DN T cells inhibited lymphoproliferation in generalized lymphoproliferative disease (GLD) mice. Furthermore, FcR? acted in a cell-intrinsic fashion to limit DN T cell accumulation by increasing the rate of apoptosis in proliferated cells. These results indicate that FcR? can confer Fas-dependent regulatory properties on LPR DN T cells, and suggest that FcR? may be a novel marker for functional DN Tregs.

SUBMITTER: Juvet SC 

PROVIDER: S-EPMC3675138 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature