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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3675-3683. Prepublished online as a Blood First Edition Paper on February 4, 2008; DOI 10.1182/blood-2008-01-130146. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-130146v1 111/7/3675    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 CrossRef Google Scholar Articles by Feng, X. Articles by Young, N. S. PubMed PubMed Citation Articles by Feng, X. Articles by Young, N. S. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro Xingmin Feng1, Sachiko Kajigaya1, Elena E. Solomou1, Keyvan Keyvanfar1, Xiuli Xu2, Nalini Raghavachari2, Peter J. Munson3, Thomas M. Herndon1, Jichun Chen1, and Neal S. Young1 1 Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD; 2 Genomics Core Facility, Pulmonary and Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD; and 3 Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, NIH, Bethesda, MD Regulatory T cells (Treg) play important roles in suppressing immune responses and maintaining tolerance. Rabbit antithymocyte globulin (rATG) and horse ATG (hATG) are widely used in the treatment of immune-mediated syndromes, but their effects on Treg are unknown. We show here that in vitro culture of normal human peripheral blood mononuclear cells (PBMCs) with a low-dose rATG resulted in marked expansion of functional Treg by converting CD4+CD25– T cells to CD4+CD25+ T cells. hATG did not expand but rather decreased Treg. Immuno-blot showed increased expression of FOXP3 and NFAT1 in CD4+CD25– and CD4+CD25+ T cells exposed to rATG. PBMCs treated with rATG displayed increased interleukin-10 in culture supernatants than those treated with hATG. Furthermore, rATG and hATG showed differences in their potential to stimulate CD4+ T cells as examined using different activation markers. Microarray revealed that rATG induced markedly different gene-expression patterns in PBMCs, compared with hATG-treated or untreated PBMCs. Our findings indicate that rATG expanded Treg, probably through transcriptional regulation by enhanced NFAT1 expression, in turn conferring CD4+CD25– T cell FOXP3 expression and regulatory activity. The therapeutic effects of rATG may occur not only because of lymphocyte depletion but also enhanced Treg cell number and function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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