Combination of donor splenocyte transfusion with blockade of γc signal synergizes to inhibit allorea

• 作 者: ZHOU Qi CHANG Sheng LIN Xing-g
• 机 构: Department of Hepatobiliary Surgery,Key Laboratory of Organ Transplantation, Institute of Organ Tran
• 出 处: 中华医学杂志（英文版）
• 发表日期: 2004年期
• 关键词: common γ chain donor splenocytes transfusion tolerance murine model

Background The common γ chain (γc) plays a critical role in regulating proliferation, differentiation, and apoptosis of peripheral T-cells. It was previously confirmed that blocking the yc signal can successfully induce transplant tolerance in a murine model. Here we investigated the potential mechanism.Methods Splenocytes from C57BL/6 mice were transfused into T-cell deficient Balb/c nude mice that were reconstituted with syngeneic wild-type T-cells labeled with 5-carboxyfluorescein diacetate succinimidyl ester (CFSE).After 24 hours, recipients received i.p. injection of mixture of anti-yc mAbs, or with isotype control IgG2a. The labeled T-cells were harvested from recipient spleens after 12 and 48 hours. T-cell proliferation and apoptosis were detected by flow cytometry.Results T-cell proliferation was markedly inhibited and apoptotic T cells could be detected at 12 hours after the mAbs injection. Proliferation was inhibited at 48 hours, but the proportion of apoptotic T-cells was not more than at 12 hours. In the control group, however, T-cells actively proliferated and no significant apoptosis was detected at either time point.Conclusions The results suggested that blockade of yc signals can synergize with donor splenocyte transfusion and lead to inhibition of antigen-specific T-cell proliferation and induction of apoptotic T-cell death. This protocol may develop a novel approach to induce donor-specific tolerance.