Cutting edge: in vivo trogocytosis as a mechanism of double negative regulatory T cell-mediated antigen-specific suppression.
Recent data have demonstrated that treatment with alphabeta-TCR(+)CD3(+)CD4(-)CD8(-)NK1.1(-) double negative (DN) regulatory T cells (Tregs) inhibits autoimmune diabetes and enhances allotransplant and xenotransplant survival in an Ag-specific fashion. However, the mechanisms whereby DN Tregs suppress Ag-specific immune responses remain largely unknown. In this study, we demonstrate that murine DN Tregs acquire alloantigen in vivo via trogocytosis and express it on their cell surface. Trogocytosis requires specific interaction of MHC-peptide on APCs and Ag-specific TCR on DN Tregs, as blocking this interaction prevents DN Treg-mediated trogocytosis. Acquisition of alloantigen by DN Tregs was required for their ability to kill syngeneic CD8(+) T cells. Importantly, DN Tregs that had acquired alloantigen were cytotoxic toward Ag-specific, but not Ag-nonspecific, syngeneic CD8(+) T cells. These data provide new insight into how Tregs mediate Ag-specific T cell suppression and may enhance our ability to use DN Tregs as a therapy for transplant rejection and autoimmune diseases.
Ford McIntyre
Megan S
MS
Multi-Organ Transplantation Program, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Canada.
Young
Kevin J
KJ
Gao
Julia
J
Joe
Betty
B
Zhang
Li
L
D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology*; D007108:Immune Tolerance; D007519:Isoantigens / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000950:Antigens, Ly; D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D007519:Isoantigens; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010446:Peptide Fragments