title: Detection of self-reactive CD8⁺ T cells with an anergic phenotype in healthy individuals.
abstract: Immunological tolerance to self requires naturally occurring regulatory T (Treg) cells. Yet how they stably control autoimmune T cells remains obscure. Here, we show that Treg cells can render self-reactive human CD8(+) T cells anergic (i.e., hypoproliferative and cytokine hypoproducing upon antigen restimulation) in vitro, likely by controlling the costimulatory function of antigen-presenting cells. Anergic T cells were naïve in phenotype, lower than activated T cells in T cell receptor affinity for cognate antigen, and expressed several coinhibitory molecules, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Using these criteria, we detected in healthy individuals anergic T cells reactive with a skin antigen targeted in the autoimmune disease vitiligo. Collectively, our results suggest that Treg cell-mediated induction of anergy in autoimmune T cells is important for maintaining self-tolerance.
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. shimon@ifrec.osaka-u.ac.jp nisihiro@ifrec.osaka-u.ac.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan.
authors.forename: Danbee
authors.initials: D
authors.lastname: Ha
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Hamaguchi
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Saito
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka565-0871, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Nishioka
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan.
authors.forename: James B
authors.initials: JB
authors.lastname: Wing
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan.
authors.forename: Dennis
authors.initials: D
authors.lastname: Adeegbe
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka565-0871, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. shimon@ifrec.osaka-u.ac.jp nisihiro@ifrec.osaka-u.ac.jp.
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D017635:Clonal Anergy; D006801:Humans; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; D011948:Receptors, Antigen, T-Cell