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Eur J Immunol. 2009 Sep;39(9):2331-6. doi: 10.1002/eji.200939688.

Dynamics of peripheral tolerance and immune regulation mediated by Treg.

Author information

1
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. shimon@frontier.kyoto-u.ac.jp

Abstract

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.

PMID:
19662638
DOI:
10.1002/eji.200939688
[Indexed for MEDLINE]
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