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B和T淋巴细胞衰减器（BTLA）与细胞毒性T淋巴细胞相关抗原4（CTLA-4）的协同作用减轻了急性T细胞介导的排斥反应，并延长了肾移植的存活时间。

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.

作者信息

Zhang Hengcheng, Wang Zijie, Zhang Jiayi, Zhang Xiang, Gui Zeping, Sun Li, Yang Haiwei, Tan Ruoyun, Gu Min

机构信息

Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Transl Androl Urol. 2020 Oct;9(5):1990-1999. doi: 10.21037/tau-20-728.

DOI:10.21037/tau-20-728
PMID:33209663
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7658142/
Abstract

BACKGROUND

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.

METHODS

We investigated the suppressive role of overexpressed BTLA and CTLA-4 . 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.

RESULTS

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.

CONCLUSIONS

The synergism of BTLA and CTLA-4 attenuated acute TCMR after kidney transplantation by suppressing T cell activation and proliferation.

摘要

背景

急性T细胞介导的排斥反应（TCMR）仍然是肾移植领域的一个主要问题。B和T淋巴细胞衰减器（BTLA）和细胞毒性T淋巴细胞相关抗原4（CTLA-4）最近被发现为共刺激分子。本研究旨在探讨BTLA和CTLA-4在TCMR中的抑制协同作用。

方法

我们研究了过表达的BTLA和CTLA-4的抑制作用。建立大鼠肾移植模型，以探讨联合过表达BTLA和CTLA-4对肾移植受者的影响。采集移植物和外周血进行肾功能、组织学、免疫组织化学和流式细胞术分析。

结果

与单一治疗组和对照组相比，联合治疗降低了白细胞介素-2（IL-2）的分泌和T细胞的增殖。联合治疗观察到移植物中间质单核细胞浸润减少，尤其是内膜动脉炎减少，外周血和移植物中T细胞数量和增殖反应显著降低。联合过表达BTLA和CTLA-4减轻了肾移植后的急性TCMR，改善了移植物功能，延长了移植物存活时间。联合治疗组对TCMR的抑制作用比单一治疗更有效。

结论

BTLA和CTLA-4的协同作用通过抑制T细胞活化和增殖减轻了肾移植后的急性TCMR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/0fe0f728bc48/tau-09-05-1990-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/b3396e32780e/tau-09-05-1990-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/204de3df5ff2/tau-09-05-1990-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/05ccbe35a4b9/tau-09-05-1990-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/0fe0f728bc48/tau-09-05-1990-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/b3396e32780e/tau-09-05-1990-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/204de3df5ff2/tau-09-05-1990-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/05ccbe35a4b9/tau-09-05-1990-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a6/7658142/0fe0f728bc48/tau-09-05-1990-f4.jpg

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