AUTHOR=Xu Heng , Yu Jizhang , Cui Jikai , Chen Zhang , Zhang Xi , Zou Yanqiang , Du Yifan , Li Yuan , Le Sheng , Jiang Lang , Xia Jiahong , Wu Jie 

TITLE=Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.710904

DOI=10.3389/fimmu.2021.710904

ISSN=1664-3224

ABSTRACT=<p>Although studies in oncology have well explored the pharmacological effects of <italic>Birc5</italic>, little is known about its role in allogeneic T-cell responses. Therefore, the present study used a mouse model of acute heart allograft rejection to investigate the protective effect and mechanism of conditional knockout of <italic>Birc5</italic> in T cells. Survivin (encoded by <italic>Birc5</italic>) was up-regulated in T cells activated <italic>in vivo</italic> and <italic>in vitro</italic>. Deletion of <italic>Birc5</italic> in T cells attenuated acute heart allograft rejection by reducing the ratio of effector to naive T cells and Th1 to Tregs. In addition, deletion of <italic>Birc5</italic> had no noticeable effect on proliferation but on apoptosis and the secretion of IFN-γ. The results revealed a significant increase in the percentage of Annexin V positive CD4<sup>+</sup> T cells in the <italic>Birc5<sup>-/-</sup></italic> group, compared to the WT. Moreover, there was significant increase in early apoptotic alloreactive T cells in <italic>Birc5</italic><sup>-/-</sup> mice and this was partly mediated by caspase-3. Furthermore, treatment with YM155 inhibited acute heart allograft rejection <italic>in vivo</italic> and increased T-cell apoptosis in healthy human PBMCs <italic>in vitro</italic>. The results highlight a potential therapeutic target for the prevention and treatment of acute transplant rejection.</p>