The synergism of B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) attenuated acute T-cell mediated rejection and prolonged renal graft survival.
The synergism of B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) attenuated acute T-cell mediated rejection and prolonged renal graft survival.
复制标题
DOI：
10.21037/tau-20-728
复制
发表时间：
2020-10
影响因子：
2
通讯作者：
Gu M
中科院分区：
文献类型：
--
作者：
Zhang H;Wang Z;Zhang J;Zhang X;Gui Z;Sun L;Yang H;Tan R;Gu M
急性T细胞介导的排斥反应（TCMR）仍然是肾移植领域的主要问题。B和T淋巴细胞衰减因子（BTLA）和细胞毒性T淋巴细胞相关抗原-4（CTLA-4）是近年来发现的共刺激分子。本研究旨在探讨BTLA和CTLA-4在中药化疗中的协同抑制作用。我们在体外研究了过表达BTLA和CTLA-4的抑制作用。建立大鼠肾移植模型，探讨BTLA和CTLA-4联合过表达对肾移植受者的影响。收集移植肾和外周血进行肾功能、组织学、免疫组化和流式细胞术分析。与单药治疗组和对照组相比，联合治疗组白细胞介素-2（IL-2）的分泌和T细胞的增殖减少。联合治疗组移植物中单核细胞浸润减少，尤其是动脉内膜炎，外周血和移植物中T细胞数量和增殖反应明显减少。联合高表达BTLA和CTLA-4可减轻移植肾急性TCMR，改善移植肾功能，延长移植肾存活时间。联合治疗组对中药耐药的抑制作用优于单药治疗组。BTLA和CTLA-4协同作用可通过抑制T细胞活化和增殖减轻肾移植后急性TCMR。
Acute T-cell mediated rejection (TCMR) continues to be a major problem in the area of kidney transplantation. The B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) were recently found costimulatory molecules. The research aims to explore the inhibitory synergism of BTLA and CTLA-4 in TCMR. We investigated the suppressive role of overexpressed BTLA and CTLA-4 in vitro. The rat kidney transplantation model was established to explore the effect of combined overexpressed BTLA and CTLA-4 in recipients of kidney transplantation. The grafts and peripheral blood were harvested for renal function, histology, immunohistochemical and flow cytometry analysis. Combination therapy decreased the secretion of interleukin-2 (IL-2) and proliferation of T cells compared to the single therapy and the control group. Decrease of interstitium monocyte infiltration and especially intimal arteritis in the graft was observed with the combination therapy, with remarkable reduction of numbers and proliferation response of T cells in peripheral blood and grafts. Combined overexpressed BTLA and CTLA-4 attenuated the acute TCMR after kidney transplantation and improved the graft function and prolonged the graft survival. The inhibiting role against TCMR in the combination therapy group was more effective than single therapy. The synergism of BTLA and CTLA-4 attenuated acute TCMR after kidney transplantation by suppressing T cell activation and proliferation.