The Common Cytokine Receptor g Chain Controls Survival of g / d T Cells

Summary We have investigated the role of common g chain ( g c )-signaling pathways for the development of T cell receptor for antigen (TCR)- g / d T cells. TCR- g / d ‐bearing cells were absent from the adult thymus, spleen, and skin of g c -deficient ( g c 2 ) mice, whereas small numbers of thymocytes expressing low levels of TCR- g / d were detected during fetal life. Recent reports have suggested that signaling via interleukin (IL)-7 plays a major role in facilitating TCR- g / d development through induction of V-J (variable-joining) rearrangements at the TCR- g locus. In contrast, we detected clearly TCR- g rearrangements in fetal thymi from g c 2 mice (which fail to signal in response to IL-7) and reduced TCR- g rearrangements in adult g c thymi. No gross defects in TCR- d or TCR- b rearrangements were observed in g c 2 mice of any age. Introduction of productively rearranged TCR V g 1 or TCR V g 1/V d 6 transgenes onto mice bearing the g c mutation did not restore TCR- g / d development to normal levels suggesting that g c -dependent pathways provide additional signals to developing g / d T cells other than for the recombination process. Bcl-2 levels in transgenic thymocytes from g c 2 mice were dramatically reduced compared to g c 1 transgenic littermates. We favor the concept that g c -dependent receptors are required for the maintenance of TCR- g / d cells and contribute to the completion of TCR- g rearrangements primarily by promoting survival of cells committed to the TCR- g / d lineage.