Dynamics of peripheral tolerance and immune regulation mediated by Treg

• Published in: European journal of immunology Vol. 39; no. 9; pp. 2331 - 2336
• Main Authors: Sakaguchi, Shimon, Wing, Kajsa, Yamaguchi, Tomoyuki
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.09.2009
• Subjects: Animals; Antigens, CD - immunology; Antigens, CD - metabolism; B7-1 Antigen - immunology; B7-1 Antigen - metabolism; B7-2 Antigen - immunology; B7-2 Antigen - metabolism; CTLA-4 Antigen; Forkhead Transcription Factors - immunology; Forkhead Transcription Factors - metabolism; Foxp3; Homeostasis - immunology; Immune homeostasis; Immune Tolerance - immunology; Medicin och hälsovetenskap; Mice; Peripheral tolerance; Signal Transduction - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Treg
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.200939688

Peripheral self‐tolerance and immune homeostasis are maintained, at least in part, by the balance between Treg and effector T cells. Naturally, arising CD25+CD4+ Treg, which express the transcription factor Foxp3, suppress the activation and proliferation of other lymphocytes in multiple ways. A CTLA‐4‐dependent suppressive mechanism is shared by every Foxp3+ Treg at any location and its disruption breaches self‐tolerance and immune homeostasis, suggesting that it is a core mechanism of suppression. Depending on the environment, Foxp3+ Treg also differentiate to exhibit additional suppressive mechanisms, including the secretion of immunosuppressive cytokines. Naïve T cells acquire Foxp3 expression and suppressive activity under certain in vivo and in vitro conditions, whereas some Foxp3+ T cells may lose Foxp3 and suppressive activity following proliferation in an IL‐2‐deficient environment. Moreover, activated effector T cells frequently secrete suppressive cytokines, such as IL‐10, in a negative feedback fashion. These findings, when taken together, indicate that peripheral immune tolerance and homeostasis are dynamically maintained by functional differentiation within the Foxp3+ population, occasional conversion between Treg and non‐Treg cells, and the interactions among them. These dynamics provide ample opportunities for immune intervention for the benefit of the host.