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¹ Department of Medicine, Division of Rheumatology and ² Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110

CORRESPONDENCE Chyi-Song Hsieh: chsieh{at}im.wustl.edu

Although regulatory T (T reg) cells are thought to develop primarily in the thymus, the peripheral events that shape the protective T reg cell population are unclear. We analyzed the peripheral CD4⁺ T cell receptor (TCR) repertoire by cellular phenotype and location in mice with a fixed TCRβ chain. We found that T reg (Foxp3⁺) cells showed a marked skewing of TCR usage by anatomical location in a manner similar to antigen-experienced (CD44^hiFoxp3^–) but not naive (CD44^loFoxp3^–) cells, even though CD44^hi and T reg cells used mostly dissimilar TCRs. This was likely unrelated to peripheral conversion, which we estimate generates only a small percentage of peripheral T reg cells in adults. Conversion was readily observed, however, during the immune response induced by Foxp3^– cells in lymphopenic hosts. Interestingly, the converted Foxp3⁺ and expanded Foxp3^– TCR repertoires were different, suggesting that generation of Foxp3⁺ cells is not an automatic process upon antigen activation of Foxp3^– T cells. Retroviral expression of these TCRs in primary monoclonal T cells confirmed that conversion did not require prior cellular conditioning. Thus, these data demonstrate that TCR specificity plays a crucial role in the process of peripheral conversion and in shaping the peripheral T reg cell population to the local antigenic landscape.

© 2008 Lathrop et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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