Development and selection of γδ T cells

Summary: Two main lineages of T cells develop in the thymus: those that express the αβ T‐cell receptor (TCR) and those that express the γδ TCR. Whereas the development, selection, and peripheral localization of newly differentiated αβ T cells are understood in some detail, these processes are less well characterized in γδ T cells. This review describes research carried out in this laboratory and others, which addresses several key aspects of γδ T‐cell development, including the decision of precursor cells to differentiate into the γδ versus αβ lineage, the ordered differentiation over the course of ontogeny of functional γδ T‐cell subsets expressing distinct TCR structures, programming of ordered Vγ gene rearrangement in the thymus, including a molecular switch that ensures appropriate Vγ rearrangements at the appropriate stage of development, positive selection in the thymus of γδ T cells destined for the epidermis, and the acquisition by developing γδ T cells of cues that determine their correct localization in the periphery. This research suggests a coordination of molecularly programmed events and cellular selection, which enables specialization of the thymus for production of distinct T‐cell subsets at different stages of development.