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

The common gamma c-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 gamma c-chain blockade on T cell activation and allograft rejection. Treatment of B6AF(1) (H-2(b/d.k)) recipient mice with anti-gamma c 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-gamma c 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 gamma c-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 gamma c-chain blockade.