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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3097-3104. Prepublished online as a Blood First Edition Paper on July 12, 2005; DOI 10.1182/blood-2005-05-1864. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: 2005-05-1864v1 106/9/3097    most recent Alert me when this article is cited Alert me if a correction is posted 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 Siegmund, K. Articles by Huehn, J. Search for Related Content PubMed PubMed Citation Articles by Siegmund, K. Articles by Huehn, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 9, 2005 Accepted June 27, 2005 Migration matters: regulatory T cell compartmentalization determines suppressive activity in vivo Kerstin Siegmund, Markus Feuerer, Christiane Siewert, Saeed Ghani, Uta Haubold, Anja Dankof, Veit Krenn, Michael P Schon, Alexander Scheffold, John B Lowe, Alf Hamann, Uta Syrbe, and Jochen Huehn* Experimentelle Rheumatologie, Charite Universitaetsmedizin, Berlin, Germany Institut fuer Pathologie, Charite Universitaetsmedizin, Berlin, Germany Rudolf Virchow Zentrum fuer Experimentelle Biomedizin und Klinik fuer Dermatologie, Julius-Maximilian-Universitaet, Wuerzburg, Germany Deutsches Rheumaforschungszentrum, Berlin, Germany Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA * Corresponding author; email: huehn{at}drfz.de. Regulatory T cells (Tregs) play a fundamental role for the suppression of different immune responses; however, compartments at which they exert suppressive functions in vivo are unknown. Although many groups described the presence of Tregs within inflammatory sites, it has not been shown that inflamed tissues are indeed the sites of active suppression of ongoing immune reactions. Here, by using E+ effector/memory-like Tregs from fucosyltransferaseVII-deficient animals, which lack E/P-selectin ligands and fail to migrate into inflamed sites, we analyzed the functional importance of appropiate Treg localization for in vivo suppressive capacity in an inflammation model. Lack of suppression by Tregs deficient in E/P-selectin ligands demonstrates that immigration into inflamed sites is a prerequiste for the resolution of inflammatory reactions in vivo, as these selectin ligands merely regulate entry into inflamed tissues. In contrast, control of proliferation of naive CD4+ T cells during the induction phase of the immune response is more efficiently exerted by the naive-like E-CD25+ Treg subset preferentially recirculating through lymph nodes when compared with its inflammation-seeking counterpart. Together, these findings provide first conclusive evidence that appropriate localization is crucial for in vivo activity of Tregs and might have significant implications for anti-inflammatory therapies targeting recruitment mechanisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Zelinskyy, K. K. Dietze, Y. P. Husecken, S. Schimmer, S. Nair, T. Werner, K. Gibbert, O. Kershaw, A. D. Gruber, T. Sparwasser, et al. 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