The common cytokine receptor gamma chain controls survival of gamma/delta T cells

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