The Common Cytokine Receptor γ Chain Controls Survival of γ/δ T Cells

We have investigated the role of common γ chain (γ_c)-signaling pathways for the development of T cell receptor for antigen (TCR)-γ/δ T cells. TCR-γ/δ–bearing cells were absent from the adult thymus, spleen, and skin of γ_c-deficient (γ_c⁻) mice, whereas small numbers of thymocytes expressing low levels of TCR-γ/δ were detected during fetal life. Recent reports have suggested that signaling via interleukin (IL)-7 plays a major role in facilitating TCR-γ/δ development through induction of V-J (variable-joining) rearrangements at the TCR-γ locus. In contrast, we detected clearly TCR-γ rearrangements in fetal thymi from γ_c⁻ mice (which fail to signal in response to IL-7) and reduced TCR-γ rearrangements in adult γ_c thymi. No gross defects in TCR-δ or TCR-β rearrangements were observed in γ_c⁻ mice of any age. Introduction of productively rearranged TCR Vγ1 or TCR Vγ1/Vδ6 transgenes onto mice bearing the γ_c mutation did not restore TCR-γ/δ development to normal levels suggesting that γ_c-dependent pathways provide additional signals to developing γ/δ T cells other than for the recombination process. Bcl-2 levels in transgenic thymocytes from γ_c⁻ mice were dramatically reduced compared to γ_c⁺ transgenic littermates. We favor the concept that γ_c-dependent receptors are required for the maintenance of TCR-γ/δ cells and contribute to the completion of TCR-γ rearrangements primarily by promoting survival of cells committed to the TCR-γ/δ lineage.