Thymic Determinants of γδ T Cell Differentiation

gamma d T cells have emerged as major sources of the proinflammatory cytokines interleukin-17 (IL-17) and interferon-gamma (IFN gamma) in multiple models of infection, cancer and autoimmune disease. However, unlike their alpha beta T cell counterparts that require peripheral activation for effector cell differentiation, gamma delta T cells instead can be 'developmentally programmed' in the thymus to generate discrete gamma delta T cell effector subsets with distinctive molecular signatures. Nonetheless, recent studies have presented conflicting viewpoints on the signals involved in thymic gamma delta T cell development and differentiation, namely on the role of both T cell receptor (TCR)-dependent and TCR-independent factors. Here we review the current data and the ongoing controversies.