International Immunology Advance Access originally published online on September 7, 2009
International Immunology 2009 21(10):1105-1111; doi:10.1093/intimm/dxp095
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review-article |
Regulatory T cells: how do they suppress immune responses?
1 Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
2 WPI Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan
3 Present address: Division of Medical inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden
4 Present address: Department of Hematology, Tohoku University School of Medicine, Sendai 980-8574, Japan
Correspondence to: S. Sakaguchi; E-mail: shimon{at}frontier.kyoto-u.ac.jp
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.
Received 15 August 2009, accepted 25 August 2009.