The role of physiological self-antigen in the acquisition and maintenance of regulatory T-cell function.
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.
Samy
Eileen T
ET
Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
Setiady
Yulius Y
YY
Ohno
Katsuhiro
K
Pramoonjago
Patcharin
P
Sharp
Colin
C
Tung
Kenneth S K
KS
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
D001324:Autoantigens