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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1199-1206. Prepublished online as a Blood First Edition Paper on April 26, 2007; DOI 10.1182/blood-2006-10-054585. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-054585v1 110/4/1199    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 Singh, N. Articles by Iwashima, M. Search for Related Content PubMed PubMed Citation Articles by Singh, N. Articles by Iwashima, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 27, 2006 Accepted April 23, 2007 Role of CD28 in fatal autoimmune disorder in scurfy mice Nagendra Singh, Phillip R. Chandler, Yoichi Seki, Babak Baban, Mayuko Takezaki, David J Kahler, David H Munn, Christian P Larsen, Andrew L Mellor, and Makio Iwashima* Immunotherapy Center, Medical College of Georgia, Augusta, GA, United States Department of Surgery, Emory Transplant Center, and Yerkes Regional Primate Research Center, Emory University School of Medicine, Augusta, GA, United States * Corresponding author; email: miwashima{at}mcg.edu. Scurfy mice develop CD4 T cell mediated lymphoproliferative disease leading to death within 4 weeks of age. The scurfy mutation causes loss of function of the foxp3 gene (foxp3sf), which is essential for development and maintenance of naturally occurring regulatory CD4 T cells (nTregs). In humans, mutations of the foxp3 gene cause immune-dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX). In most IPEX patients and also in scurfy mice, T cells show hyper-reactivity and levels of Th1 and Th2 associated cytokines are substantially elevated. Here, we report that removal of CD28 expression rescued scurfy mice from early death. Longer term surviving CD28 deficient scurfy mice still suffered from lymphoproliferative disorder but their CD4 T cells showed decreased IFN- and no sign of IL-4, IL-10, hyper-production. Furthermore, injection of CTLA4-Ig to block CD28-B7 interactions substantially improved the survival of scurfy mice by blocking effector T cell differentiation. These data support the hypothesis that CD28-B7 interactions play a critical role in the etiology of lethal autoimmune disease in scurfy mice by stimulating the differentiation of antigen-activated naive T cells into effector T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Lahl, C. T. Mayer, T. Bopp, J. Huehn, C. Loddenkemper, G. Eberl, G. Wirnsberger, K. Dornmair, R. Geffers, E. Schmitt, et al. Nonfunctional Regulatory T Cells and Defective Control of Th2 Cytokine Production in Natural Scurfy Mutant Mice J. Immunol., November 1, 2009; 183(9): 5662 - 5672. [Abstract] [Full Text] [PDF] A. Liston, L.-F. Lu, D. O'Carroll, A. Tarakhovsky, and A. Y. Rudensky Dicer-dependent microRNA pathway safeguards regulatory T cell function J. Exp. Med., September 1, 2008; 205(9): 1993 - 2004. [Abstract] [Full Text] [PDF]

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