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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1056-1062. Prepublished online as a Blood First Edition Paper on October 13, 2005; DOI 10.1182/blood-2005-08-3088. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-08-3088v1 107/3/1056    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 Setiady, Y. Y. Articles by Tung, K. S. K. Search for Related Content PubMed PubMed Citation Articles by Setiady, Y. Y. Articles by Tung, K. S. K. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Physiologic self antigens rapidly capacitate autoimmune disease-specific polyclonal CD4+CD25+ regulatory T cells Yulius Y. Setiady, Katsuhiro Ohno, Eileen T. Samy, Harini Bagavant, Hui Qiao, Colin Sharp, Jin Xiong She, and Kenneth S. K. Tung From the Departments of Pathology, Microbiology, and Internal Medicine, University of Virginia, Charlottesville, VA; and Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA. Studies on CD4+CD25+ regulatory T cells (Tregs) with transgenic T-cell receptors indicate that Tregs may receive continuous antigen (Ag) stimulation in the periphery. However, the consequence of this Ag encounter and its relevance to physiologic polyclonal Treg function are not established. In autoimmune prostatitis (EAP) of the day-3 thymectomized (d3tx) mice, male Tregs suppressed EAP 3 times better than Tregs from female mice or male mice without prostates. Importantly, the superior EAP-suppressing function was acquired after a 6-day exposure to prostate Ag in the periphery, unaffected by sex hormones. Thus, a brief exposure of physiologic prostate Ag capacitates peripheral polyclonal Tregs to suppress EAP. In striking contrast, autoimmune ovarian disease (AOD) was suppressed equally by male and female Tregs. We now provide evidence that the ovarian Ag develops at birth, 14 days earlier than prostate Ag, and that male Tregs respond to neonatal ovarian Ag in the Treg recipients to gain AOD-suppressing capacity. When d3tx female recipients were deprived of ovarian Ag in the neonatal period, AOD was suppressed by female but not by male Tregs, whereas dacryoadenitis was suppressed by both. We conclude that the physiologic autoAg quickly and continuously enhances disease-specific polyclonal Treg function to maintain self-tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Regulatory T cells: timing is everything Joachim L. Schultze Blood 2006 107: 857. [Full Text] [PDF] This article has been cited by other articles: E. T. Samy, K. M. Wheeler, R. J. Roper, C. Teuscher, and K. S. K. Tung Cutting Edge: Autoimmune Disease in Day 3 Thymectomized Mice Is Actively Controlled by Endogenous Disease-Specific Regulatory T Cells J. Immunol., April 1, 2008; 180(7): 4366 - 4370. [Abstract] [Full Text] [PDF] Q.-G. Ruan, K. Tung, D. Eisenman, Y. Setiady, S. Eckenrode, B. Yi, S. Purohit, W.-P. Zheng, Y. Zhang, L. Peltonen, et al. The Autoimmune Regulator Directly Controls the Expression of Genes Critical for Thymic Epithelial Function J. Immunol., June 1, 2007; 178(11): 7173 - 7180. [Abstract] [Full Text] [PDF]

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