Foreign antigen-specific Foxp3+ regulatory T cells expand with immunization and limit Th1 polarization by Foxp3− conventional cells specific for the same antigen

Abstract

Abstract The CD4+ T cell repertoire contains thousands of populations, each with antigen receptors specific for a different major histocompatibility complex class II (MHCII)-bound foreign peptide. Before exposure to the foreign peptide, an average population in a mouse consists of about 100 naïve Foxp3− conventional cells and 10 Foxp3+ regulatory T (Treg) cells. After infection containing the peptide, the population increases several hundred-fold and contains Foxp3− and Foxp3+ effector cells. Because conventional T cells have been reported to generate Treg cells and vice versa, it is not clear which precursors generate which effector cells. Using progeny-tracing systems, we found that Foxp3− conventional cells and Foxp3+ Treg cells specific for the same peptide:MHCII ligand proliferated at the same rate after immunization. Foxp3− naïve cells generated only Foxp3− effector cells, and Foxp3− naïve cells generated primarily Foxp3+ effectors cells. The Treg cells suppressed the Th1 differentiation of the Foxp3− cells but did not cause them to become Treg cells. These results demonstrate that Foxp3− and Foxp3+ naïve T cells are remarkably lineage-committed during the primary response to infection, and although their progeny interact, this interaction does not result in lineage instability.