Thymic development of gut microbiota-specific T cells

Humans and their microbiota have coevolved a mutually beneficial relationship, with the human host providing a hospitable environment for the microbes, and the microbiota providing many benefits including nutritional benefits and protection from pathogen infection. Maintaining this relationship requires careful immune balance to contain commensals within the lumen while limiting inflammatory anti-commensal responses. A number of groups describe T cell antigen-specific recognition of intestinal microbes. While the local environment shapes effector cell differentiation it is unclear how microbiota-specific T cells are educated in the thymus. Here we identify that early life intestinal colonization leads to trafficking of microbial antigens from the intestine to the thymus by intestinal dendritic cells (DCs) which then expand microbiota-specific T cells. Once in the periphery, microbiota-specific T cells have pathogenic potential, or can protect against related pathogens. In this way, the developing microbiota shapes and expands the thymic and peripheral T cell repertoire, allowing for enhanced recognition of intestinal microbes and pathogens.