Dynamics of peripheral tolerance and immune regulation mediated by Treg

Eur J Immunol. 2009 Sep;39(9):2331-6. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Homeostasis / immunology
  • Immune Tolerance / immunology*
  • Mice
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CTLA-4 Antigen
  • Cd86 protein, mouse
  • Ctla4 protein, mouse
  • Forkhead Transcription Factors