The impact of circulating dendritic cells on the development and differentiation of thymocytes.

Central tolerance is established through the negative selection of self-reactive thymocytes and the induction of T-regulatory cells (T-regs). A role for thymic epithelial cells in mediating both negative selection and T-reg induction has been clearly shown. The role of thymic dendritic cells (DCs) in these processes has not been clearly determined but has been the focus of recent studies. Thymic DCs include two conventional DC (cDC) subtypes, CD8(lo)Sirpalpha(hi/+) (CD8(lo)Sirpalpha(+) herein) and CD8(hi)Sirpalpha(lo/-) (CD8(hi)Sirpalpha(-) herein). It has been shown that these DC subsets have distinct developmental origins, the CD8(hi)Sirpalpha(-) cDCs developing intra-thymically and the CD8(lo)Sirpalpha(+) migrating into the thymus from the periphery. Furthermore, an important role for thymic DCs in the induction of T-regs has been shown. In this review, the role of DCs in the development and education of T cells in the thymus will be reviewed, with emphasis on the role of circulatory DCs in mediating these processes.