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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.
Submitted August 1, 2005
Department of Pathology, University of Virginia, Charlottesville, VA, USA * Corresponding author; email: kst7k{at}virginia.edu.
Studies on CD4+CD25+ regulatory T cells (Treg) with transgenic T cell receptors indicate that Treg may receive continuous antigen (Ag) stimulation in the periphery. However, the consequence of this Ag encounter and its relevance to physiological polyclonal Treg function are not established. In autoimmune prostatitis (EAP) of the day 3 thymectomized (d3tx) mice, male Treg suppressed 3-times better than Treg from female or male without prostate. 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 physiological prostate Ag capacitates peripheral polyclonal Treg to suppress EAP. In strike contrast, autoimmune ovarian disease (AOD) was suppressed equally by male and female Treg. We now provided evidence that the ovarian Ag developed at birth, 14 days earlier than prostate Ag, and that male Treg responded 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 Treg, whereas dacryoadenitis was suppressed by both. We conclude that the physiological autoAg quickly and continuously enhances disease-specific polyclonal Treg function in order to maintain self tolerance.
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