Ly-6A is critical for the function of double negative regulatory T cells.
We have recently demonstrated that CD3+CD4-CD8- double negative (DN) T cells can down-regulate allogeneic immune responses both in vitro and in vivo by killing activated syngeneic CD8+ T cells. The goal of this study was to identify molecules that are crucial for DN T cell-mediated suppression. We demonstrate that Ly-6A (Sca-1) is highly expressed on DN T cells. Incubation with IL-10 significantly reduced Ly-6A expression and the function of DN T cells. DN T cell-mediated killing was significantly reduced when Ly-6A was blocked.Ly-6A-deficient mice showed an accelerated allograft rejection when compared to wild-type controls. Furthermore we demonstrate that pretransplantation donor lymphocyte infusion (DLI) led to activation and proliferation of recipient DN T cells and prolongation of bm1-->B6 skin allograft survival. However, when the recipients were deficient in Ly-6A, the beneficial effect of DLI on allograft survival was abolished. Moreover, deficiency in Ly-6A did not affect the activation and proliferation of DN T cells. Rather, it impaired the ability of DN T cells to kill activated anti-donor CD8+ T cells. Taken together, our data indicate that Ly-6A plays a crucial role in DN T cell-mediated regulation in vitro and in vivo, perhaps by enhancing DN-CD8+ T cell signaling.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, Toronto, Canada.
Zhu-Xu
ZX
Zhang
William L
WL
Stanford
Li
L
Zhang
D000818:Animals; D000950:Antigens, Ly / Q000502:physiology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006084:Graft Rejection; D016753:Interleukin-10 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*; D014184:Transplantation, Homologous
D000950:Antigens, Ly; D015704:CD4 Antigens; D016827:CD8 Antigens; D016753:Interleukin-10