Arsenic Trioxide Induces T Cell Apoptosis and Prolongs Islet Allograft Survival in Mice. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Transplantation. Volume 99:Issue 9(2015)
• Publication Date: 2015-09
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000000735
• Languages: English
• ISSNs: 0041-1337

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background</title> <p>T cell–mediated immune rejection is a key barrier to islet transplantation. Preliminary studies have shown that arsenic trioxide (As<sub>2</sub>O<sub>3</sub>) can inhibit T cell responses and prolong heart allograft survival. Here, we sought to investigate the possibility of using As<sub>2</sub>O<sub>3</sub> to prolong islet allograft survival in an acute rejection model of Balb/c to C57B/6 mice.</p> </sec> <sec> <title>Methods</title> <p>Recipient mice were treated with As<sub>2</sub>O<sub>3</sub> 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 As<sub>2</sub>O<sub>3</sub> 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 As<sub>2</sub>O<sub>3</sub>-treated T cells.</p> </sec> <sec> <title>Results</title> <p>We found that As<sub>2</sub>O<sub>3</sub> prolonged islet allograft survival by reducing inflammatory reactions, influencing cytokine synthesis and secretion and T-cell subset proportions, and inhibiting T-cell responses. Furthermore, As<sub>2</sub>O<sub>3</sub> and rapamycin showed a synergistic effect in suppressing islet allotransplant rejection.</p> </sec> <sec> <title>Conclusions</title> <p>Arsenic trioxide may prevent allograft rejection by inhibiting T-cell proliferation and inducing T-cell apoptosis.</p> </sec> </abstract>