title: Regulatory T cells: how do they suppress immune responses?
abstract: Regulatory T cells (Tregs), either natural or induced, suppress a variety of physiological and pathological immune responses. One of the key issues for understanding Treg function is to determine how they suppress other lymphocytes at the molecular level in vivo and in vitro. Here we propose that there may be a key suppressive mechanism that is shared by every forkhead box p3 (Foxp3)(+) Treg in vivo and in vitro in mice and humans. When this central mechanism is abrogated, it causes a breach in self-tolerance and immune homeostasis. Other suppressive mechanisms may synergistically operate with this common mechanism depending on the environment and the type of an immune response. Further, Treg-mediated suppression is a multi-step process and impairment or augmentation of each step can alter the ultimate effectiveness of Treg-mediated suppression. These findings will help to design effective ways for controlling immune responses by targeting Treg suppressive functions.
authors.affiliation: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan. shimon@frontier.kyoto-u.ac.jp
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Kajsa
authors.initials: K
authors.lastname: Wing
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Onishi
authors.forename: Paz
authors.initials: P
authors.lastname: Prieto-Martin
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1