Reaching maturity: Thymic γδ T cell differentiation in mice and humans

γδ T cells are promising players in immunotherapy because of pleiotropic functions, many of which can be preprogrammed in the thymus. Here, we review the cellular and molecular mechanisms that underlie γδ T cell development in the mouse and human thymi, focusing on their acquisition of diverse cytotoxic or cytokine-secreting functions and their dependence on interactions with the specialized thymic epithelium. We discuss the most recent findings and models that inform our understanding of γδ T cell differentiation and may affect the development of γδ T cell-based immunotherapies.