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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2877-2886. Prepublished online as a Blood First Edition Paper on December 21, 2004; DOI 10.1182/blood-2004-07-2505. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-07-2505v1 105/7/2877    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kleinewietfeld, M. Articles by Falk, K. Search for Related Content PubMed PubMed Citation Articles by Kleinewietfeld, M. Articles by Falk, K. Related Collections Chemokines, Cytokines, and Interleukins Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CCR6 expression defines regulatory effector/memory-like cells within the CD25+CD4+ T-cell subset Markus Kleinewietfeld, Fabiola Puentes, Giovanna Borsellino, Luca Battistini, Olaf Rötzschke, and Kirsten Falk From the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; and Laboratory of Neuroimmunology, Santa Lucia Foundation, Rome, Italy. Regulatory CD25+CD4+ T cells (Treg cells) are a central element of peripheral tolerance. Little is known, however, about phenotypic and functional characteristics of these cells with regard to memory. In this study we show that the chemokine receptor CCR6 is expressed on a distinct subset of mouse Treg cells. Similar to their CD25- counterparts, CCR6+ Treg cells exhibit markers of activation, memory, and expansion that are indicative for an effector-memory function. They are memory-like cells, generated in vivo from CCR6-CD25+ T cells after the encounter of antigen. As conventional CD25- effector-memory T cells, they have a high turnover rate and, in contrast to CCR6- Treg cells, they respond rapidly to restimulation in vitro with up-regulation of interleukin 10. CCR6+ Treg cells are enriched in the peripheral blood and accumulate in the central nervous system after induction of experimental autoimmune encephalomyelitis (EAE). This subset therefore seems to represent a population of regulatory effector-memory T cells (TREM), destined to control potentially destructive immune responses directly in inflamed tissues. Importantly, these cells are also present in humans. Here the expression of CCR6 fully cosegregates with CD45RO, an established marker of human memory T cells. 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