Cutting edge: normal regional lymph node enrichment of antigen-specific regulatory T cells with autoimmune disease-suppressive capacity.
Natural CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) effectively prevent autoimmune disease development, but their role in maintaining physiological tolerance against self-Ag of internal organs is not yet defined. In this study, we quantified disease-specific Treg (DS-Treg) as Treg that preferentially suppress one autoimmune disease over another in day 3 thymectomized recipients. A striking difference was found among individual lymph nodes (LN) of normal mice; Treg from draining LN were 15-50 times more efficient than those of nondraining LN at suppressing autoimmune diseases of ovary, prostate, and lacrimal glands. The difference disappeared upon auto-Ag ablation and returned upon auto-Ag re-expression. In contrast, the CD4(+)CD25(-) effector T cells from different individual LN induced multiorgan inflammation with comparable organ distribution. We propose that peripheral tolerance for internal organs relies on the control of autoreactive effector T cells by strategic enrichment of Ag-specific Treg in the regional LN.
Wheeler
Karen M
KM
Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
Samy
Eileen T
ET
Tung
Kenneth S K
KS
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D015704:CD4 Antigens / Q000096:biosynthesis; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis*; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000276:immunology; D010049:Ovarian Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D017634:Self Tolerance / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D053645:Interleukin-2 Receptor alpha Subunit