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 (DSTreg) 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 effectorTcells by strategic enrichment of Ag-specific Treg in the regional LN.