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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
 
Arthritis Res Ther. 2004; 6(5): 215–222.
Published online Aug 11, 2004. doi:  10.1186/ar1226
PMCID: PMC546291
Regulating the immune system: the induction of regulatory T cells in the periphery
Jane H Buckner1 and Steven F Zieglercorresponding author2
1Diabetes Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
2Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
corresponding authorCorresponding author.
Steven F Ziegler: sziegler/at/vmresearch.org
Received March 31, 2004; Revisions requested May 12, 2004; Revised July 19, 2004; Accepted July 21, 2004.
Abstract
The immune system has evolved a variety of mechanisms to achieve and maintain tolerance both centrally and in the periphery. Central tolerance is achieved through negative selection of autoreactive T cells, while peripheral tolerance is achieved primarily via three mechanisms: activation-induced cell death, anergy, and the induction of regulatory T cells. Three forms of these regulatory T cells have been described: those that function via the production of the cytokine IL-10 (T regulatory 1 cells), transforming growth factor beta (Th3 cells), and a population of T cells that suppresses proliferation via a cell-contact-dependent mechanism (CD4+CD25+ TR cells). The present review focuses on the third form of peripheral tolerance – the induction of regulatory T cells. The review will address the induction of the three types of regulatory T cells, the mechanisms by which they suppress T-cell responses in the periphery, the role they play in immune homeostasis, and the potential these cells have as therapeutic agents in immune-mediated disease.
Keywords: interleukin-10, regulatory T cell, suppression, transforming growth factor beta, tolerance
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