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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1726-1734. Prepublished online as a Blood First Edition Paper on November 19, 2007; DOI 10.1182/blood-2007-08-106526. This Article Full Text (PDF) All Versions of this Article: blood-2007-08-106526v1 111/3/1726    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 Ruzek, M. C Articles by Garman, R. D Search for Related Content PubMed PubMed Citation Articles by Ruzek, M. C Articles by Garman, R. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 20, 2007 Accepted November 16, 2007 Characterization of in vitro anti-murine thymocyte globulin-induced regulatory T cells which inhibit graft-versus-host disease in vivo Melanie C Ruzek*, James S Waire, Deborah Hopkins, Gina LaCorcia, Jennifer Sullivan, Bruce L Roberts, Susan M Richards, Sharon R Nahill, John M Williams, Abraham Scaria, John Dzuris, Srinivas Shankara, and Richard D Garman Immunology and Clinical Laboratory Sciences, Biologics R&D, Genzyme Corporation, Framingham, MA, United States Applied Genomics, Science Research, Genzyme Corporation, Framingham, MA, United States Immune Mediated Disease Biology, Science Research, Genzyme Corporation, Framingham, MA, United States Molecular Biology, Science Research, Genzyme Corporation, Framingham, MA, United States * Corresponding author; email: melanie.ruzek{at}genzyme.com. Anti-thymocyte/lymphocyte globulins are polyclonal anti-human T cell antibodies used clinically to treat acute transplant rejection. These reagents deplete T cells, but a rabbit-anti-human thymocyte globulin has also been shown to induce regulatory T cells in vitro. To examine whether anti-thymocyte globulin-induced regulatory cells might be functional in vivo, we generated a corresponding rabbit anti-murine thymocyte globulin (mATG) and tested its ability to induce regulatory cells in vitro and whether those cells can inhibit acute graft-versus-host disease (GVHD) in vivo upon adoptive transfer. In vitro mATG induces a population of CD4+CD25+ cells that express several cell surface molecules representative of regulatory T cells. These cells do not express Foxp3 at either the protein or mRNA level, but do show suppressive function both in vitro and in vivo when adoptively transferred into a model of GVHD. These results demonstrate that in a murine system, anti-thymocyte globulin induces cells with suppressive activity that also function in vivo to protect against acute GVHD. Thus, in both murine and human systems, anti-thymocyte globulins not only deplete T cells, but also appear to generate regulatory cells. The in vitro generation of regulatory cells by anti-thymocyte globulins could provide additional therapeutic modalities for immune mediated disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Huang, M. Parker, C. Xia, R. Peng, C. Wasserfall, T. Clarke, L. Wu, T. Chowdhry, M. Campbell-Thompson, J. Williams, et al. Rabbit Polyclonal Mouse Antithymocyte Globulin Administration Alters Dendritic Cell Profile and Function in NOD Mice to Suppress Diabetogenic Responses J. Immunol., April 15, 2009; 182(8): 4608 - 4615. [Abstract] [Full Text] [PDF] X. Feng, S. Kajigaya, E. E. Solomou, K. Keyvanfar, X. Xu, N. Raghavachari, P. J. Munson, T. M. Herndon, J. Chen, and N. S. Young Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro Blood, April 1, 2008; 111(7): 3675 - 3683. [Abstract] [Full Text] [PDF]

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