| First Author | Xu H | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 710904 | PubMed ID | 34421916 |
| Mgi Jnum | J:314246 | Mgi Id | MGI:6765819 |
| Doi | 10.3389/fimmu.2021.710904 | Citation | Xu H, et al. (2021) Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis. Front Immunol 12:710904 |
| abstractText | Although studies in oncology have well explored the pharmacological effects of Birc5, 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 Birc5 in T cells. Survivin (encoded by Birc5) was up-regulated in T cells activated in vivo and in vitro. Deletion of Birc5 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 Birc5 had no noticeable effect on proliferation but on apoptosis and the secretion of IFN-gamma. The results revealed a significant increase in the percentage of Annexin V positive CD4(+) T cells in the Birc5(-/-) group, compared to the WT. Moreover, there was significant increase in early apoptotic alloreactive T cells in Birc5 (-/-) mice and this was partly mediated by caspase-3. Furthermore, treatment with YM155 inhibited acute heart allograft rejection in vivo and increased T-cell apoptosis in healthy human PBMCs in vitro. The results highlight a potential therapeutic target for the prevention and treatment of acute transplant rejection. |
