The common cytokine receptor γ chain controls survival of γ/δ T cells

Abstract

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.