Anti-γc and anti-IL-2Rβ mAbs inhibit donor-antigen reactive T cells proliferation and induce H-Y skin graft acceptance in murine model

Objective The is an To investigate whether blocking common cytokine receptor γ chain (γc) signals can induce transplant tolerance.Methods The animals were randomly divided into 3 groups ( n =7 in each). GroupⅠ (control group): C57BL/6 female mice only received H-Y skin grafts. Group Ⅱ: Female recipients received transfusion of splenocytes (5×10 6 cells) from syngeneic male mice on day 7 before H-Y skin grafting. Group Ⅲ: Following donor-splenocytes pretreatment, on the day 2 and 4, female recipients received intraperitoneal injection of mixture of anti-IL-2Rβ mAb (TM-β1) and anti-γc mAbs (i.e., 4G3, 3E12 and TUGm2, 0.5 mg , respectively). On the day 7, H-Y skin grafts were performed.Results All recipients treated with mixture of mAbs in combination with donor-splenocytes transfusion accepted H-Y skin grafts over 100 days without evidence of rejection. Group Ⅰ rejected grafts within 35 days after grafting (MST= 33.42 days) and group Ⅱ rejected grafts within 17 days after grafting (MST= 14.71 days). There were statistically significant diffe- rences among the groups ( P 0.01 ).Conclusion Blockade of γc signaling in combination with donor- splenocytes pretreatment can markedly prolong H-Y skin graft survival, which might be associated with inhibition of antigen-specific T cell proliferation and induction of apoptosis.