The ICOS–ICOSL pathway tunes thymic selection

Negative selection of developing T cells plays a significant role in T‐cell tolerance to self‐antigen. This process relies on thymic antigen‐presenting cells which express both self‐antigens and cosignaling molecules. Inducible T‐cell costimulator (ICOS) belongs to the CD28 family of cosignaling molecules and binds to ICOS ligand (ICOSL). The ICOS signaling pathway plays important roles in shaping the immune response to infections, but its role in central tolerance is less well understood. Here we show that ICOSL is expressed by subsets of thymic dendritic cells and medullary thymic epithelial cells as well as thymic B cells. ICOS expression is upregulated as T cells mature in the thymus and correlates with T‐cell receptor signal strength during thymic selection. We also provide evidence of a role for ICOS signaling in mediating negative selection. Our findings suggest that ICOS may fine‐tune T‐cell receptor signals during thymic selection contributing to the generation of a tolerant T‐cell population. We show that inducible T‐cell costimulator (ICOS) expression is upregulated as T cells mature in the thymus and that its ligand is expressed by important thymic antigen‐presenting cell populations that regulate negative selection of autoreactive T cells. We provide evidence of a role for the ICOS–ICOS ligand pathway in fine‐tuning T‐cell receptor signals during thymic selection contributing to the generation of a tolerant T‐cell population. Our observations add an additional layer of complexity to the network of cosignaling molecules potentially involved in sculpting the T‐cell receptor repertoire.