Instructive Cues of Thymic T Cell Selection

A high diversity of alpha beta T cell receptors (TCRs), capable of recognizing virtually any pathogen but also self-antigens, is generated during T cell development in the thymus. Nevertheless, a strict developmental program supports the selection of a self-tolerant T cell repertoire capable of responding to foreign antigens. The steps of T cell selection are controlled by cortical and medullary stromal niches, mainly composed of thymic epithelial cells and dendritic cells. The integration of important cues provided by these specialized niches, including (a) the TCR signal strength induced by the recognition of self-peptide-MHC complexes, (b) costimulatory signals, and (c) cytokine signals, critically controls T cell repertoire selection. This review discusses our current understanding of the signals that coordinate positive selection, negative selection, and agonist selection of Foxp3(+) regulatory T cells. It also highlights recent advances that have unraveled the functional diversity of thymic antigen-presenting cell subsets implicated in T cell selection.

Automated summary

During thymic development, signals provided by specific cells control the selection of T cells, resulting in the generation of a T cell repertoire capable of responding to foreign antigens while tolerating self-antigens. This review summarizes our current understanding of the signals involved in the selection of regulatory T cells and highlights the functional diversity of thymic antigen-presenting cell subsets implicated in T cell selection.