Anti-γ Chain and Anti-IL-2Rβ mAbs in Combination With Donor Splenocyte Transfusion Induce H-Y Skin Graft Acceptance in Murine Model

Background. The common cytokine receptor gamma chain signals regulate proliferation, differentiation, and apoptosis of peripheral T cells. Objective. To investigate whether simultaneous blockade of IL-2R beta and gamma chain signaling in combination with donor splenocyte transfusion (DST) induces transplant tolerance. Materials and Methods. C57BL/6 (H-2b) mice were randomly divided into 5 groups. In group 1, female mice received only H-Y skin grafts. In group 2, female mice received transfused splenocytes (5 X 10(6) cells) from syngeneic male mice on day 7 before H-Y skin grafting. In group 3, on days 2 and 4 after DST, female mice received intraperitoneal injections of a mixture of anti-IL-2R beta monoclonal antibody (mAb) and anti-gamma chain mAbs (4G3, 3E12, and TUGm2; 0.5 mg). After DST, group 4 received an intraperitoneal injection of the mixture of anti-gamma chain mAbs, and group 5 received intraperitoneal injection of anti-IL-2R beta mAb (TM-beta 1). On day 7, H-Y skin grafting was performed. Results. Group 3 recipients accepted H-Y skin grafts for more than 100 days compared with group 1 (mean survival time [MST], 33.42 days), group 2 (MST, 14.71 days), group 4 (MST, 58.71 days), and group 5 (MST, 17.29 days). Statistical differences (P < .05) were observed between any 2 groups except groups 2 and 5. Conclusion. Blockade of gamma chain signaling rather than IL-2R beta signaling combined with DST prolongs H-Y skin graft survival. Simultaneous blockade of IL-2R beta and gamma chain signaling may strengthen this effect.