Prolongation of allograft survival by administration of mAb specific for the three subunits of IL-2 receptor.

Abstract

The IL-2 receptor (IL-2R) gamma chain, the so-called common gamma (gamma(c)) chain, which is shared with multiple cytokine receptors, plays important roles in the immune system. Here we assessed the immunosuppressive ability of mAb specific for the gamma(c) chain in induction of cytotoxic T lymphocytes (CTL) and allograft rejection in combination with mAb specific for the alpha and beta chains of IL-2R. CBA/N (H-2k) mice were injected i.p. with allogeneic splenocytes from BALB/c (H-2d) mice, and then administered with combinations of anti-IL-2R alpha, anti-IL-2R beta and anti-gamma(c) mAb or a control mAb. Addition of anti-gamma(c) mAb together with anti-IL-2R alpha and anti-IL-2R beta mAb induced a complete inhibition of CTL response. The numbers and populations of CD4+ CD8- and CD4- CD8+ T cells were not significantly affected by administration of the three anti-IL-2R mAb, whereas NK cells were completely depleted in spleens of mice treated with the anti-IL-2R mAb. Furthermore, skin allograft survival was also significantly prolonged by administration of the three anti-IL-2R mAb. These results suggest that the anti-gamma(c) mAb in combination with anti-IL-2R alpha and anti-IL-2R beta mAb is capable of suppressing induction of CTL and NK cells, resulting in prolongation of skin allograft survival.