Regulatory T Cell Generation During Lifetime, a Central Tolerance Difference and Later Organism Homeostasis Repercussion

Abstract

Regulatory T cells (Tregs) permit an individual to host a large T cell repertoire while avoiding potentially pathologic autoreactivity. The population of Tregs generated in perinatal mice differs from that produced in adults, transcriptome and TCR repertoire. The function of these early Tregs remains quite enigmatic. We wondered whether thymic Treg progenitors differ in perinatal and adult mice. A time-course revealed that the ratio of the two T regulatory T cell progenitors (Foxp3+CD25- to Foxp3-CD25+) changed considerably during early life. In addition, thymic medullary epithelial cells from perinatal and adult mice showed differences in the antigen presentation machinery, as well as in their repertoires of cytokines and costimulatory molecules, according to RNA-seq analysis. Interestingly, depletion experiments using Foxp3-DTR mice revealed differential recovery of the Treg populations in different parenchymal tissues, suggesting that adult mice might not be able to generate these populations.