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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0706474

Received for publication July 26, 2006.

Accepted for publication September 12, 2006.

Article

Regulatory T cell-mediated suppression: potential role of ICER

Josef Bodor *@, Zoltan Fehervari {dagger}, Betty Diamond *, and Shimon Sakaguchi {ddagger}

*Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA; {dagger}Department of Pathology, University of Cambridge, Cambridge, UK; and {ddagger}Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

@ To whom correspondence should be addressed. E-mail: jb2562{at}columbia.edu.


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Abstract

How regulatory T (TR) cells dampen T cell responses remains unclear. Multiple modes of action have been proposed, including cell contact-dependent and/or cytokine-dependent mechanisms. Suppression may involve direct contact between TR cells and responder T cells. Alternatively, TR cells may act on dendritic cells to reduce their ability to prime T cells by modulating costimulation, inducing the secretion of suppressive cytokines or the increase of tryptophan metabolism. Here, we review emerging, novel mechanisms involved in contact-dependent, TR-mediated suppression of IL-2 production in responder CD25- T lymphocytes and the potential involvement of inducible cAMP early repressor in this suppression. Finally, cytokines such as TGF-{beta} and IL-10, produced by TR cells or other cells, may exert local suppression, which can be conveyed by basic mechanism(s) acting in a similar manner as contact-dependent, TR-mediated suppression.

Key Words: transcriptional repressor • inhibitory receptor • immune regulation




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