| First Author | Juvet SC | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 6 | Pages | e65253 |
| PubMed ID | 23762329 | Mgi Jnum | J:203195 |
| Mgi Id | MGI:5525177 | Doi | 10.1371/journal.pone.0065253 |
| Citation | Juvet SC, et al. (2013) FcRgamma controls the fas-dependent regulatory function of lymphoproliferative double negative T cells. PLoS One 8(6):e65253 |
| abstractText | Patients with autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferation (LPR) mice are deficient in Fas, and accumulate large numbers of alphabeta-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, FcRgamma, plays an important role in mediating innate immune responses. We have shown previously that a significant proportion of DN T cells express FcRgamma, and that this molecule is required for TCR transgenic DN T cells to suppress allogeneic immune responses. Whether FcRgamma 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 FcRgamma(+), but not FcRgamma(-) 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 FcRgamma expression did not allow LPR DN T cells to inhibit the expansion of Fas-deficient cells within the LPR context, adoptive transfer of FcRgamma(+), but not FcRgamma(-), DN T cells inhibited lymphoproliferation in generalized lymphoproliferative disease (GLD) mice. Furthermore, FcRgamma 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 FcRgamma can confer Fas-dependent regulatory properties on LPR DN T cells, and suggest that FcRgamma may be a novel marker for functional DN Tregs. |
