Abstract
The precise steps of iNKT subset differentiation in the thymus and periphery have been controversial. We demonstrate here that the small proportion of thymic iNKT and mucosal associated invariant T cells that express CCR7 represent a multi-potent progenitor pool that gives rise to effector subsets within the thymus. Using intra-thymic labeling, we also showed that CCR7+ iNKT cells emigrate from the thymus in a Klf2 dependent manner, and undergo further maturation after reaching the periphery. Ccr7 deficiency impaired differentiation of iNKT effector subsets and localization to the medulla. Parabiosis and intra-thymic transfer showed that thymic NKT1 and NKT17 were resident-they were not derived from and did not contribute to the peripheral pool. Finally, each thymic iNKT effector subset produces distinct factors that influence T cell development. Our findings demonstrate how the thymus is both a source of iNKT progenitors and a unique site of tissue dependent effector cell differentiation.