title: The role and mechanisms of double negative regulatory T cells in the suppression of immune responses.
abstract: Accumulating evidence has demonstrated that regulatory T (Treg) cells play an important role in the maintenance of immunologic self-tolerance and in down-regulating various immune responses. Thus, there has recently been an increasing interest in studying the biology of Treg cells as well as their potential application in treating immune diseases. Many types of Treg cell subsets have been reported in a variety of disease models. Among these subsets, alpha beta TCR(+)CD3(+)CD4(-)CD8(-) double negative (DN) Treg cells are defined by their capability of inhibiting immune responses via directly killing effector T cells in an antigen specific fashion. Furthermore, DN Treg cells have been shown to develop regulatory activity after encountering specific antigens, partially mediated by the acquisition of MHC-peptide complexes from antigen presenting cells (APCs). The presentation of acquired alloantigens on DN T cells allows for the specific interaction between DN Treg cells and alloantigen reactive effector T cells. Once the DN Treg and target cells have come into contact, killing is then mediated by Fas/Fas-ligand interactions, and perhaps through other unidentified pathways. Further characterization of the functions, molecular expression and mechanisms of activation of DN Treg cells will help in the development of novel therapies to induce antigen specific tolerance to self and foreign antigens.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Toronto General Research Institute, University Health Network, Toronto, M5G 2C4, Canada.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Chen
authors.forename: Megan S
authors.initials: MS
authors.lastname: Ford
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Young
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D053222:Fas Ligand Protein; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006649:Histocompatibility Antigens; D007519:Isoantigens; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D019014:fas Receptor