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

αβ and γδ T cells are thought to arise from a common precursor in the thymus but play distinct roles in pathogen resistance. Although conventional αβ T cells exit the thymus in a naive state and acquire effector function in the periphery, the effector fate of many γδ 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 γδ T cells, as well as the apparent linkage to V_γ 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_γ 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.