title: Physiologic self antigens rapidly capacitate autoimmune disease-specific polyclonal CD4+ CD25+ regulatory T cells.
abstract: 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.
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Yulius Y
authors.initials: YY
authors.lastname: Setiady
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ohno
authors.forename: Eileen T
authors.initials: ET
authors.lastname: Samy
authors.forename: Harini
authors.initials: H
authors.lastname: Bagavant
authors.forename: Hui
authors.initials: H
authors.lastname: Qiao
authors.forename: Colin
authors.initials: C
authors.lastname: Sharp
authors.forename: Jin Xiong
authors.initials: JX
authors.lastname: She
authors.forename: Kenneth S K
authors.initials: KS
authors.lastname: Tung
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D003607:Dacryocystitis / Q000276:immunology / Q000473:pathology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000276:immunology; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D009869:Oophoritis / Q000276:immunology / Q000473:pathology; D011472:Prostatitis / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D001324:Autoantigens; D012739:Gonadal Steroid Hormones