Origins of γδ T Cell Effector Subsets: A Riddle Wrapped in an Enigma

alpha beta and gamma delta T cells are thought to arise from a common precursor in the thymus but play distinct roles in pathogen resistance. Although conventional alpha beta T cells exit the thymus in a naive state and acquire effector function in the periphery, the effector fate of many gamma delta T cells is specified in the thymus and exhibits limited plasticity thereafter. This review describes the current models that have been proposed to explain the acquisition of effector fate by gamma delta T cells, as well as the apparent linkage to V gamma gene usage. The two predominant models are the predetermination model, which suggests that effector fate is determined prior to TCR expression, perhaps in association with the developmental timing of V gamma rearrangement, and the TCR-dependence model, which proposes that the nature of the TCR signal, particularly its intensity or duration, plays an important role in influencing effector fate.