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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 (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 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 Feng, X. Articles by Young, N. S. Search for Related Content PubMed PubMed Citation Articles by Feng, X. Articles by Young, N. S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 3, 2008 Accepted February 1, 2008 Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro Xingmin Feng*, Sachiko Kajigaya, Elena E. Solomou, Keyvan Keyvanfar, Xiuli Xu, Nalini Raghavachari, Peter J. Munson, Thomas M. Herndon, Jichun Chen, and Neal S. Young Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, United States Genomics Core Facility, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD, United States Mathematical and Statistical Computing Lab, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, MD, United States * Corresponding author; email: fengx2{at}nhlbi.nih.gov. Regulatory T cells (Treg) play important roles in suppressing immune responses and maintaining tolerance. Rabbit anti-thymocyte 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 (PBMC) 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. Immunoblot showed increased expression of FOXP3 and NFAT1 in CD4+CD25- and CD4+CD25+ T cells exposed to rATG. PBMC treated with rATG displayed increased IL-10 in culture supernatants than that 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 PBMC, as compared with hATG-treated or untreated PBMC. Our findings indicate that rATG expanded Treg, probably through transcriptional regulation by enhanced NFAT1 expression, in turn conferring CD4+CD25- T cells FOXP3 expression and regulatory activity. The therapeutic effects of rATG may occur not only due to lymphocyte depletion but to enhanced Treg cell number and function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. A. De Serres, M. H. Sayegh, and N. Najafian Immunosuppressive Drugs and Tregs: A Critical Evaluation! Clin. J. Am. Soc. Nephrol., October 1, 2009; 4(10): 1661 - 1669. [Abstract] [Full Text] [PDF] E K Geissler and H J Schlitt Immunosuppression for liver transplantation Gut, March 1, 2009; 58(3): 452 - 463. [Abstract] [Full Text] [PDF]

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