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Blood, 15 January 2006, Vol. 107, No. 2, pp. 619-627. Prepublished online as a Blood First Edition Paper on September 22, 2005; DOI 10.1182/blood-2005-06-2277. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-06-2277v1 107/2/619    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 Firan, M. Articles by Siegelman, M. H. Search for Related Content PubMed PubMed Citation Articles by Firan, M. Articles by Siegelman, M. H. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Suppressor activity and potency among regulatory T cells is discriminated by functionally active CD44 Mihail Firan, Sohita Dhillon, Pila Estess, and Mark H. Siegelman From the Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX. CD4CD25+ regulatory T cells are fundamental to the maintenance of peripheral tolerance and have great therapeutic potential. However, efforts in this regard have been hampered by limiting cell numbers in vivo, an anergic phenotype in vitro, and a rudimentary understanding of the molecular basis for the functional state of CD4CD25+ regulatory T cells (Treg cells). Here we show heterogeneity of suppressor activity among activated CD4CD25+ Treg cells and that, within this population, the functionally active, hyaluronan-binding form of CD44 (CD44act) is strikingly correlated with superior suppressor activity. Within 16 hours after in vitro activation, CD44act can discriminate enhanced suppressive function in in vitro proliferation assays and in an in vivo bone marrow engraftment model. The expression of other surface markers and that of Foxp3 are similar irrespective of hyaluronan binding and associated degree of suppressor potency. Furthermore, CD44act is induced on resting CD4CD25+ cells in vivo by allogeneic stimulation, with similar functional consequences. These results reveal a cell-surface marker that delineates functional activity within a population of activated CD4CD25+ regulatory T cells, thereby providing a potential tool for identifying regulatory activity and enriching for maximal suppressor potency. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. C. Ruzek, J. S. Waire, D. Hopkins, G. LaCorcia, J. Sullivan, B. L. Roberts, S. M. Richards, S. R. Nahill, J. M. Williams, A. Scaria, et al. Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo Blood, February 1, 2008; 111(3): 1726 - 1734. [Abstract] [Full Text] [PDF] I. Fernandez, R. Zeiser, H. Karsunky, N. Kambham, A. Beilhack, K. Soderstrom, R. S. Negrin, and E. Engleman CD101 Surface Expression Discriminates Potency Among Murine FoxP3+ Regulatory T Cells J. Immunol., September 1, 2007; 179(5): 2808 - 2814. [Abstract] [Full Text] [PDF] F. Behrens, A. Himsel, S. Rehart, J. Stanczyk, B. Beutel, S. Y Zimmermann, U. Koehl, B. Moller, S. Gay, J. P Kaltwasser, et al. Imbalance in distribution of functional autologous regulatory T cells in rheumatoid arthritis Ann Rheum Dis, September 1, 2007; 66(9): 1151 - 1156. [Abstract] [Full Text] [PDF] P. L. Bollyky, J. D. Lord, S. A. Masewicz, S. P. Evanko, J. H. Buckner, T. N. Wight, and G. T. Nepom Cutting Edge: High Molecular Weight Hyaluronan Promotes the Suppressive Effects of CD4+CD25+ Regulatory T Cells J. Immunol., July 15, 2007; 179(2): 744 - 747. [Abstract] [Full Text] [PDF] G. M. Venturi, R. M. Conway, D. A. Steeber, and T. F. Tedder CD25+CD4+ Regulatory T Cell Migration Requires L-Selectin Expression: L-Selectin Transcriptional Regulation Balances Constitutive Receptor Turnover J. Immunol., January 1, 2007; 178(1): 291 - 300. [Abstract] [Full Text] [PDF] R. A. Clark and T. S. Kupper IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells isolated from human skin Blood, January 1, 2007; 109(1): 194 - 202. [Abstract] [Full Text] [PDF]

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