title: The role of physiological self-antigen in the acquisition and maintenance of regulatory T-cell function.
abstract: The CD4+ CD25+ regulatory T cells (Tregs) are efficient regulators of autoimmunity, but the mechanism remains elusive. We summarize recent data for the conclusion that disease-specific Tregs respond to tissue antigens to maintain physiological tolerance and prevent autoimmunity. First, polyclonal Tregs from antigen-positive donors suppress autoimmune ovarian disease (AOD) or experimental autoimmune prostatitis in day 3 thymectomized (d3tx) mice more efficiently than Tregs from antigen-negative donors. Second, Tregs of antigen-negative adult mice respond to cognate antigen in vivo and rapidly gain disease-specific Treg function. Third, in d3tx female recipients devoid of neonatal ovarian antigens, only female Tregs suppressed AOD; the male Tregs gain AOD-suppressing function by responding to the ovarian antigen in the recipients and mask the supremacy of female Tregs in AOD suppression. Fourth, when Tregs completely suppress AOD, the ovary-draining lymph node is the only location with evidence of profound and persistent (but reversible) host T-cell suppression. Fifth, from these nodes, highly potent AOD-suppressing Tregs are retrievable. We conclude that self-tolerance involves the continuous priming of Tregs by autoantigens, and in autoimmune disease suppression, the effector T-cell response is continuously negated by potent disease-specific Tregs that accumulate at the site of autoantigen presentation.
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Eileen T
authors.initials: ET
authors.lastname: Samy
authors.forename: Yulius Y
authors.initials: YY
authors.lastname: Setiady
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ohno
authors.forename: Patcharin
authors.initials: P
authors.lastname: Pramoonjago
authors.forename: Colin
authors.initials: C
authors.lastname: Sharp
authors.forename: Kenneth S K
authors.initials: KS
authors.lastname: Tung
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D007165:Immunosuppression Therapy; D051379:Mice; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation
chemical_list: D001324:Autoantigens