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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4594-4601. Prepublished online as a Blood First Edition Paper on March 11, 2004; DOI 10.1182/blood-2003-08-2897. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2897v1 103/12/4594    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 Mamura, M. Articles by Letterio, J. J. Search for Related Content PubMed PubMed Citation Articles by Mamura, M. Articles by Letterio, J. J. Related Collections Cell Adhesion and Motility Signal Transduction Gene Expression Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CD28 disruption exacerbates inflammation in Tgf-1-/- mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-1 Mizuko Mamura, WoonKyu Lee, Timothy J. Sullivan, Angelina Felici, Anastasia L. Sowers, James P. Allison, and John J. Letterio From the Laboratory of Cell Regulation and Carcinogenesis and the Laboratory of Molecular Biology, National Institutes of Health, Center for Cancer Research, Bethesda; Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, MD; and Howard Hughes Medical Institute, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley. Tgf-1-/- mice develop a progressive, lethal, inflammatory syndrome, but mechanisms leading to the spontaneous activation of Tgf-1-/- T cells remain unclear. Here we show the disruption of CD28 gene expression accelerates disease in Tgf-1-/- mice, and we link this increase in severity to a reduction in the number of CD4+CD25+ regulatory T cells. CD4+CD25+ T cells develop normally in Tgf-1-/- mice and display characteristic expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), E7 integrin, and Foxp3. Adoptive transfer of Tgf-1-/- splenocytes to Tgf-1+/+/Rag2-/- mice induced an autoimmune inflammatory disease with features similar to those of the Tgf-1-/- phenotype, and disease transfer was accelerated by the depletion of Tgf-1-/- CD4+CD25+ T cells from donor splenocytes. Cotransfer of Tgf- 1-/- CD4+CD25+ T cells clearly attenuated disease in Rag2-/- recipients of CD25+-depleted Tgf-1-/- spleen and lymph node cells, but suppression was incomplete when compared with Tgf-1+/+ CD4+CD25+ T cells. These data demonstrate that CD4+CD25+ regulatory T cells develop in complete absence of endogenous transforming growth factor-1 (TGF-1) expression and that autocrine TGF-1 expression is not essential for these cells to suppress inflammation in vivo. (Blood. 2004;103:4594-4601) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. H. Wrzesinski, Y. Y. Wan, and R. A. Flavell Transforming Growth Factor-{beta} and the Immune Response: Implications for Anticancer Therapy Clin. Cancer Res., September 15, 2007; 13(18): 5262 - 5270. [Abstract] [Full Text] [PDF] S. Hinz, L. Pagerols-Raluy, H.-H. Oberg, O. Ammerpohl, S. Grussel, B. Sipos, R. Grutzmann, C. Pilarsky, H. Ungefroren, H.-D. 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