Anti-gamma chain and anti-IL-2Rbeta 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-2Rbeta 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-2Rbeta 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-2Rbeta mAb (TM-beta1). 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-2Rbeta signaling combined with DST prolongs H-Y skin graft survival. Simultaneous blockade of IL-2Rbeta and gamma chain signaling may strengthen this effect.