Combination of donor splenocyte transfusion with blockade of γc signal synergizes to inhibit alloreactive T-cell proliferation and induces apoptosis  

作　　者：ZHOU Qi CHANG Sheng LIN Xing-guang XIANG Fu-li CHEN Zhong-hua 

机构地区：[1]Department of Hepatobiliary Surgery, First Affiliated Hospital, SunYat-sen University, Guangzhou, Guangdong 510080, China [2]Key Laboratory of Organ Transplantation, Ministry of Education/Ministry of Health Institute of Organ Transplantation, TongjiHospital, Tongji Medical College, Huazhong University of Scienceand Technology, Wuhan, Hubei 430030, China

出　　处：《Chinese Medical Journal》2011年第18期2874-2878,共5页中华医学杂志（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China （No. 30500468）.

摘　　要：Background The common y 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-γc 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 γc 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.Background The common y 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-γc 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 γc 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.

关 键 词：common γ chain donor splenocytes transfusion tolerance murine model 

分 类 号：R[医药卫生]