Development and selection of γδ T cells

Two main lineages of T cells develop in the thymus: those that express the alpha beta T- cell receptor ( TCR) and those that express the gamma delta TCR. Whereas the development, selection, and peripheral localization of newly differentiated alpha beta T cells are understood in some detail, these processes are less well characterized in gamma delta T cells. This review describes research carried out in this laboratory and others, which addresses several key aspects of gamma delta T- cell development, including the decision of precursor cells to differentiate into the gamma delta versus alpha beta lineage, the ordered differentiation over the course of ontogeny of functional gamma delta T- cell subsets expressing distinct TCR structures, programming of ordered V gamma gene rearrangement in the thymus, including a molecular switch that ensures appropriate V gamma rearrangements at the appropriate stage of development, positive selection in the thymus of gamma delta T cells destined for the epidermis, and the acquisition by developing gamma delta 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. Two main lineages of T cells develop in the thymus: those that express the alpha beta T-cell receptor (TCR) and those that express the gamma delta TCR. Whereas the development, selection, and peripheral localization of newly differentiated alpha beta T cells are understood in some detail, these processes are less well characterized in gamma delta T cells. This review describes research carried out in this laboratory and others, which addresses several key aspects of gamma delta T-cell development, including the decision of precursor cells to differentiate into the gamma delta versus alpha beta lineage, the ordered differentiation over the course of ontogeny of functional gamma delta T-cell subsets expressing distinct TCR structures, programming of ordered V gamma gene rearrangement in the thymus, including a molecular switch that ensures appropriate V gamma rearrangements at the appropriate stage of development, positive selection in the thymus of gamma delta T cells destined for the epidermis, and the acquisition by developing gamma delta 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.