Journal of Leukocyte Biology
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Published online before print June 29, 2006
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0206095

Received for publication February 13, 2006.
Revised April 4, 2006.
Accepted for publication April 26, 2006.

Article

Development and function of naturally occurring CD4+CD25+ regulatory T cells

Akiko Toda and Ciriaco A. Piccirillo @

Department of Microbiology and Immunology, McGill University, Montreal, Canada

@ To whom correspondence should be addressed. E-mail: ciro.piccirillo{at}mcgill.ca.


  Abstract

The immune system has evolved numerous mechanisms of peripheral T cell immunoregulation, including a network of regulatory T (Treg) cells, to modulate and down-regulate immune responses at various times and locations and in various inflammatory circumstances. Amongst these, naturally occurring CD4+CD25+ Treg cells (nTreg) represent a major lymphocyte population engaged in the dominant control of self-reactive T responses and maintaining tolerance in several models of autoimmunity. CD4+CD25+ Treg cells differentiate in the normal thymus as a functionally distinct subpopulation of T cells bearing a broad T cell receptor repertoire, endowing these cells with the capacity to recognize a wide range of self and nonself antigen specificities. The generation of CD4+CD25+ Treg cells in the immune system is genetically controlled, influenced by antigen recognition, and various signals, in particular, cytokines such as interleukin-2 and transforming growth factor-{beta}1, control their activation, expansion, and suppressive effector activity. Functional abrogation of these cells in vivo or genetic defects that affect their development or function unequivocally promote the development of autoimmune and other inflammatory diseases in animals and humans. Recent progress has shed light on our understanding of the cellular and molecular basis of CD4+CD25+ Treg cell-mediated immune regulation. This article discusses the relative contribution of CD4+CD25+ nTreg cells in the induction of immunologic self-tolerance and provides a comprehensive overview of recent finding regarding the functional properties and effector mechanism of these cells, as revealed from various in vitro and in vivo models.

Key Words: IL-2 • Foxp3 • TGF-{beta}1 • diabetes • colitis • infection




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