title: Characterization of the immunoregulatory function of human TCR-αβ+ CD4- CD8- double-negative T cells.
abstract: Regulatory T cells (Tregs) play an important role in the maintenance of immune tolerance to self-antigens and are involved in modulating immune responses in autoimmunity, transplant rejection, and tumor immunity. Recently, a novel subset of TCR-αβ(+) CD4(-) CD8(-) (double negative, DN) T cells has been described to specifically suppress T-cell responses in mice. Here, we demonstrate that human DN T cells are highly potent suppressors of both CD4(+) and CD8(+) T-cell responses. In contrast to naturally occurring CD4(+) CD25(+) Tregs, DN T cells have to be activated by antigen-presenting cells (APCs) to induce their regulatory potential. The suppressive activity of DN T cells is neither mediated indirectly by modulation of APCs nor by competition for T-cell growth factors. Furthermore, DN T-cell-mediated suppression toward responder T cells is TCR dependent and requires novel protein synthesis. In contrast to murine DN T cells, which eliminate effector T cells via Fas/FasL or perforin/granzyme, human DN T cells suppress proliferation of responder T cells by cell contact-dependent mechanisms. Taken together, our data indicate that human DN T cells exert strong immunosuppressive effects on both CD4(+) and CD8(+) T cells and may serve as a new therapeutic approach to treat autoimmunity and transplant rejection.
authors.affiliation: Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Voelkl
authors.forename: Regina
authors.initials: R
authors.lastname: Gary
authors.forename: Andreas
authors.initials: A
authors.lastname: Mackensen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta