Cutting edge:: Self-peptides drive the peripheral expansion of CD4+CD25+ regulatory T cells

CD4(+) CD25(+) regulatory T cell selection is initiated by high-specificity interactions with self-peptides in the thymus, although how these cells respond to cytokine-derived signals and to re-exposure to self-peptide:MHC complexes in the periphery is not well understood. We have used a transgenic mouse system, in which the peptide that induces thymic selection of a clonal population of CD4(+) CD25(+) regulatory T cells is known, to show that CD4(+) CD25(+) T cells proliferate in response to their selecting seLf-peptide in vivo. Moreover, they do not proliferate in response to lymphopenia in the absence of the selecting self-peptide, reacting a low level of expression of the high affinity receptor for IL-7 (CD127) relative to conventional CD4(+) T cells. That their selecting self-peptide is both requiredfor and promotes the peripheral expansion of CD4(+) CD25(+) regulatory T cells may direct their accumulation in sites where the self-peptide is expressed.