Fcr Gamma Controls The Fas-Dependent Regulatory Function Of Lymphoproliferative Double Negative T Cells

PLOS ONE(2013)

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摘要
Patients with autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferation (LPR) mice are deficient in Fas, and accumulate large numbers of alpha beta-TCR+, CD4(-), CD8(-) double negative (DN) T cells. The function of these DN T cells remains largely unknown. The common gamma subunit of the activating Fc receptors, FcR gamma, plays an important role in mediating innate immune responses. We have shown previously that a significant proportion of DN T cells express FcR gamma, and that this molecule is required for TCR transgenic DN T cells to suppress allogeneic immune responses. Whether FcR gamma 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 gamma(+), but not FcR gamma(-) 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 gamma expression did not allow LPR DN T cells to inhibit the expansion of Fas-deficient cells within the LPR context, adoptive transfer of FcR gamma(+), but not FcR gamma(-), DN T cells inhibited lymphoproliferation in generalized lymphoproliferative disease (GLD) mice. Furthermore, FcR gamma 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 gamma can confer Fas-dependent regulatory properties on LPR DN T cells, and suggest that FcR gamma may be a novel marker for functional DN Tregs.
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关键词
cell proliferation,gene expression regulation,adoptive transfer
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