FcRγ Controls the Fas-Dependent Regulatory Function of Lymphoproliferative Double Negative T Cells

FcRγ Controls the Fas-Dependent Regulatory Function of Lymphoproliferative Double Negative T Cells

Patients with autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferation (LPR) mice are deficient in Fas, and accumulate large numbers of αβ-TCR(+), CD4(-), CD8(-) double negative (DN) T cells. The function of these DN T cells remains largely unknown. The common γ subunit of the activating Fc receptors, FcRγ, plays an important role in mediating innate immune responses. We have show...

Autocrine IFNγ Controls the Regulatory Function of Lymphoproliferative Double Negative T Cells

TCRαβ(+) CD4(-)CD8(-)NK(-) double negative T cells (DN T cells) can act as regulatory T cells to inhibit allograft rejection and autoimmunity. Their role in graft-versus-host disease and mechanisms of suppression remain elusive. In this study, we demonstrate that DN T cells can inhibit CD4(+) T cell-mediated GVHD in a semi-allogeneic model of bone marrow transplantation. Furthermore, we present...

The Immune Regulatory Function of Lymphoproliferative Double Negative T Cells In Vitro and In Vivo

Lymphoproliferative (lpr) mice, which lack functional Fas receptor expression and develop autoimmune lymphoproliferative disease, have an accumulation of T cell receptor-alphabeta(+)CD4(-)CD8(-) (double negative T cells [DNTC]) in the periphery. The function of the accumulating DNTC is not clear. In this study we demonstrate that B6/lpr DNTC can dose dependently kill syngeneic CD8(+) and CD4(+)...

FAS-L, IL-10, and double-negative CD4 CD8 TCR / T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function

Aude Magerus-Chatinet,1,2 Marie-Claude Stolzenberg,1,2 Maria S. Loffredo,1,2 Bénédicte Neven,1-3 Catherine Schaffner,1,2 Nicolas Ducrot,1,2 Peter D. Arkwright,4 Brigitte Bader-Meunier,3 José Barbot,5 Stéphane Blanche,3 Jean-Laurent Casanova,2,3,6 Marianne Debré,3 Alina Ferster,7 Claire Fieschi,8 Benoit Florkin,9 Claire Galambrun,10 Olivier Hermine,2-3,11 Olivier Lambotte,12 Eric Solary,13 Carol...

FcR Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function