Blocking the common γ-chain of cytokine receptors induces T cell apoptosis and long-term islet allograft survival

The common γc-chain is an essential signaling component shared by all known T cell growth factor (TCGF) receptors (i.e., IL-2, IL-4, IL-7, IL-9, and IL-15). In the present study, we have studied the effect of γc-chain blockade on T cell activation and allograft rejection. Treatment of B6AF₁ (H-2(b/d.k)) recipient mice with anti-γc mAbs induced long-term survival of DBA/2 (H-2(d)) islet allografts (>150 days, n = 8), whereas control Ab- treated mice rejected the islet allografts within 17 days (n = 6). The state of engraftment induced by the anti-γc mAbs was remarkably stable, as recipient mice bearing the primary islet allografts accepted a second DBA/2 islet allograft without further immunosuppression and systemic administration of high doses of IL-2Ig fusion protein failed to provoke rejection. Blocking the γc-chain inhibited T cell proliferation and induced T cell apoptosis by repressing expression of Bcl-2. Our data suggest that one means of inducing T cell apoptosis and stable allograft survival can be achieved via γc-chain blockade.