Expression of the immune regulator Aire during the first few weeks of life is necessary and sufficient to prevent autoimmunity in Aire−/− mice. In Science, Yang et al. show that perinatal Aire expression promotes the generation of regulatory T cells (Treg) with a functional, transcriptome and activation profile distinct from that of Treg cells produced in adult mice. Depletion of Treg cells on days 0–10 of life induces autoimmunity similar to that of Aire−/− mice, which is rescued only by perinatal wild-type Treg cells and not by adult wild-type or perinatal Aire−/− Treg cells. Perinatal Treg cells are more proliferative, are more suppressive, have a higher expression of genes associated with Treg effector function and persist in adult mice. The perinatal medullary thymic epithelial cells (mTECs) have a different, more diverse peptide repertoire compared to adult mTECs that is due to more effective loading into the MHC class II antigen–binding groove (owing to a lower ratio of the DO:DM molecular chaperones), resulting in a different TCR repertoire in the two age groups. Thus, perinatal Treg cells have different repertoires, and may also guard distinct tissues or organs, compared to adult Treg cells.

Science (19 March 2015) doi:10.1126/science.aaa7017