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(+) T cells from wild-type B6 mice through Fas/Fas ligand interactions in vitro. We also demonstrate that B6/lpr DNTC that are activated and expand in vivo are able to specifically down-regulate allogeneic immune responses mediated by syngeneic Fas(+)CD4(+) and CD8(+) T cells in vivo. B6/lpr DNTC that have been preactivated in vivo by infusion of either class I- (bm1) or class II- (bm12) mismatched allogeneic lymphocytes are able to specifically enhance the survival of bm1 or bm12, but not third-party skin allografts when adoptively transferred into naive B6(+/+) mice. These findings clearly demonstrate that B6/lpr DNTC have a potent immune regulatory function in vitro and in vivo. They also provide new insights into the mechanisms involved in the development of autoimmune disease in lpr mice.
Ford
Megan S
MS
Department of Laboratory Medicine and Pathobiology, University of Toronto, Multi Organ Transplantation Program, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada.
Young
Kevin J
KJ
Zhang
Zhuxu
Z
Ohashi
Pamela S
PS
Zhang
Li
L
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D006085:Graft Survival / Q000276:immunology; D066298:In Vitro Techniques; D007519:Isoantigens; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007519:Isoantigens; D008562:Membrane Glycoproteins; D019014:fas Receptor