Gao Chang, Jiang Jie, Ma Pengfei, Cheng Panpan, Lian Yinlong, Zhao Bin, Li Chenglin, Peng Yuanzheng, Wang Feiyu, Lin Yingying, Jin Ning, Li Jiali, Wang Lumin, Li Qing, Leng Yun, Xia Junjie, Qi Zhongquan
1 Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, China. 2 Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen City, Fujian Province, China. 3 State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Transplantation. 2015 Sep;99(9):1796-806. doi: 10.1097/TP.0000000000000735.
T cell-mediated immune rejection is a key barrier to islet transplantation. Preliminary studies have shown that arsenic trioxide (As2O3) can inhibit T cell responses and prolong heart allograft survival. Here, we sought to investigate the possibility of using As2O3 to prolong islet allograft survival in an acute rejection model of Balb/c to C57B/6 mice.
Recipient mice were treated with As2O3 and/or rapamycin after islet allograft transplantation. At day 10 after transplantation, the graft, spleen, lymph nodes, and blood of the recipient mice were recovered for analysis. In vitro, to further examine the mechanism underlying As2O3 protection of islet allografts against T cell-mediated rejection, mixed lymphocyte reaction and apoptosis analyses of T cells were performed. The phosphorylation levels of IκBα and p38 were also evaluated to confirm the proliferation and apoptosis of As2O3-treated T cells.
We found that As2O3 prolonged islet allograft survival by reducing inflammatory reactions, influencing cytokine synthesis and secretion and T-cell subset proportions, and inhibiting T-cell responses. Furthermore, As2O3 and rapamycin showed a synergistic effect in suppressing islet allotransplant rejection.
Arsenic trioxide may prevent allograft rejection by inhibiting T-cell proliferation and inducing T-cell apoptosis.
T细胞介导的免疫排斥是胰岛移植的关键障碍。初步研究表明，三氧化二砷（As2O3）可抑制T细胞反应并延长心脏同种异体移植的存活时间。在此，我们试图研究在Balb/c到C57B/6小鼠的急性排斥模型中使用As2O3延长胰岛同种异体移植存活时间的可能性。
胰岛同种异体移植后，对受体小鼠进行As2O3和/或雷帕霉素治疗。移植后第10天，收集受体小鼠的移植物、脾脏、淋巴结和血液进行分析。在体外，为进一步研究As2O3保护胰岛同种异体移植免受T细胞介导排斥的机制，进行了混合淋巴细胞反应和T细胞凋亡分析。还评估了IκBα和p38的磷酸化水平，以确认As2O3处理的T细胞的增殖和凋亡情况。
我们发现，As2O3通过减少炎症反应、影响细胞因子合成和分泌以及T细胞亚群比例，抑制T细胞反应，从而延长了胰岛同种异体移植的存活时间。此外，As2O3和雷帕霉素在抑制胰岛同种异体移植排斥方面显示出协同作用。
三氧化二砷可能通过抑制T细胞增殖和诱导T细胞凋亡来预防同种异体移植排斥。
