Peripheral expansion of thymus-derived regulatory cells in anti-myelin basic protein T cell receptor transgenic mice.

CD4+ regulatory T cells (Treg) play an indispensable role in tolerance to peripheral antigens, but the origin of the Treg pool in the adult remains unclear. Thus, while thymic commitment of Treg has been demonstrated, evidence also exists for the peripheral recruitment of naïve tissue-specific T cells into Treg functions. Anti-myelin basic protein TCR transgenic mice spontaneously develop autoimmune encephalomyelitis when "monoclonal", but are protected by adoptive transfer of CD4+ cells from wild-type donors. We have now used this transfer system to investigate whether previously infused Treg can recruit transgenic T cells to regulatory functions. The results show that transgenic T cells from protected animals did not transfer tolerance to secondary recipients, and that elimination of donor Treg in protected recipients resulted in rapid onset of disease. In addition, Treg-containing T cell susbsets were highly enriched for proliferating cells in vivo, which was also the case for CD4+CD25+ T cells in normal animals. These observations thus exclude peripheral differentiation of Treg in this particular system, and indicate that expansion of thymically committed cells ensures the maintenance of the peripheral Treg pool in the adult.