Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells

Despite a growing appreciation of gamma delta T cell contributions to numerous immune responses, the mechanisms that underpin their thymic development remain poorly understood. Here, using precursor/product relationships, we identify thymic stages in two distinct developmental pathways that generate gamma delta T cells pre-committed to subsequent secretion of either IL-17A or IFN gamma. Importantly, this framework for tracking gamma delta T cell development has permitted definitive assessment of TCR gamma delta signal strength in commitment to gamma delta T cell effector fate; increased TCR gamma delta signal strength profoundly prohibited the development of all IL-17A-secreting gamma delta T cells, regardless of V gamma usage, but promoted the development of gamma delta progenitors along the IFN gamma pathway. This clarifies the recently debated role of TCR gamma delta signal strength in commitment to distinct gamma delta T cell effector fates and proposes an alternate methodology for the study of gamma delta T cell development.