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Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Expression of the transcription factor FoxP3 is the hallmark of regulatory T cells that play a crucial role in dampening immune responses. A comparison of the development and phenotype of FoxP3+ T cells in relation to the expression of conventional MHC molecules facilitated the identification of several distinct lineages of naive and effector/memory populations of Foxp3+ T cells. One subpopulation of effector/memory Foxp3+ T cells develops in the thymic medulla, whereas the second is thymic independent. Both lineages display a distinct activated phenotype, undergo extensive steady-state proliferation, home to sites of acute inflammation, and are unique in their capacity to mediate Ag-nonspecific suppression of T cell activation directly ex vivo. Effector FoxP3+ T cells may act as a sentinel of tolerance, providing a first line of defense against potentially harmful responses by rapidly suppressing immunity to peripheral self-Ags.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.
2 Address correspondence and reprint requests to Dr. Ethan M. Shevach, National Institutes of Health, Building 10, Room 11N315, 10 Center Drive, MSC-1892, Bethesda, MD 20892-1892. E-mail address: eshevach{at}niaid.nih.gov
3 Abbreviations used in this paper: LN, lymph node; 7-AAD, 7-aminoactinomycin D; HA, hemagglutinin; 
2m, 2-microglobulin; KLRG1, killer cell lectin-like receptor G1.
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