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T细胞免疫反应cDNA 7在急性移植物抗宿主病病理过程中的作用

Role of T cell immune response cDNA 7 on the pathology of acute graft-versus-host disease.

作者信息

Zhu Feng, Xu Yanqiu, Fan Xiaohui, Zhang Fan, Wang Dong, Qiao Jianlin, Zhu Shengyun, Zhao Kai, Pan Bin, Chen Chong, Zeng Lingyu, Li Zhenyu, Xu Kailin

机构信息

Blood Disease Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

出版信息

Oncol Lett. 2020 Dec;20(6):300. doi: 10.3892/ol.2020.12163. Epub 2020 Sep 28.

DOI:10.3892/ol.2020.12163
PMID:33101494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7577082/
Abstract

Activation of T lymphocytes is the initiating factor of the occurrence of acute graft-versus-host disease (aGVHD), and cytotoxic T lymphocyte antigen-4 (CTLA-4) is the inhibitory receptor for activating T cells. T cell immune response cDNA 7 (TIRC7) is considered an upstream regulator of CTLA-4; however, little is understood regarding the effects of TIRC7 on the regulation of CTLA-4 in aGVHD. The purpose of the present study was to evaluate the regulatory effects of TIRC7 on aGVHD, mainly in the pathology. Recipient mice were exposed to a preconditioning dose of 7.5 Gy irradiation on the day of the transplantation and were divided into the following groups: Blank control group, bone marrow transplantation control group, total body irradiation group, mild-moderate aGVHD group and severe aGVHD group. According to the different administration of CTLA-4 and TIRC7 monoclonal antibodies, the mild-moderate and severe aGVHD groups were randomly divided into the hematopoietic stem cell transplantation (HSCT) and HSCT + CTLA-4/TIRC7 groups. Recipient mice were sacrificed at different time points post-HSCT for histopathological analysis by hematoxylin and eosin staining. Compared with the control and other experimental groups, the mice in the combined CTLA-4 and TIRC7 group exhibited ameliorated pathological injury, and lower pathology scores of the liver, lung and intestine. These data revealed that intraperitoneal injection of anti-TIRC7 and/or anti-CTLA-4 monoclonal antibody into mice could effectively alleviate the severity of aGVHD.

摘要

T淋巴细胞的激活是急性移植物抗宿主病（aGVHD）发生的起始因素，细胞毒性T淋巴细胞抗原4（CTLA-4）是激活T细胞的抑制性受体。T细胞免疫反应cDNA 7（TIRC7）被认为是CTLA-4的上游调节因子；然而，关于TIRC7在aGVHD中对CTLA-4调节作用的了解甚少。本研究的目的是评估TIRC7对aGVHD的调节作用，主要是在病理学方面。在移植当天，受体小鼠接受7.5 Gy的预处理剂量照射，并分为以下几组：空白对照组、骨髓移植对照组、全身照射组、轻-中度aGVHD组和重度aGVHD组。根据CTLA-4和TIRC7单克隆抗体的不同给药方式，将轻-中度和重度aGVHD组随机分为造血干细胞移植（HSCT）组和HSCT + CTLA-4/TIRC7组。在HSCT后的不同时间点处死受体小鼠，通过苏木精和伊红染色进行组织病理学分析。与对照组和其他实验组相比，联合CTLA-4和TIRC7组的小鼠病理损伤减轻，肝脏、肺和肠道的病理评分降低。这些数据表明，向小鼠腹腔注射抗TIRC7和/或抗CTLA-4单克隆抗体可有效减轻aGVHD的严重程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/5730a0ec30a1/ol-20-06-12163-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/b0706d2eab27/ol-20-06-12163-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/b6de906fac38/ol-20-06-12163-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/4cb9fdbb6428/ol-20-06-12163-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/8652e52e8a48/ol-20-06-12163-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/f3232da9dea8/ol-20-06-12163-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/8b43ff5b83db/ol-20-06-12163-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/91eddf9528f3/ol-20-06-12163-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/efb179d70b3a/ol-20-06-12163-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/5730a0ec30a1/ol-20-06-12163-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/b0706d2eab27/ol-20-06-12163-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/b6de906fac38/ol-20-06-12163-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/4cb9fdbb6428/ol-20-06-12163-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/8652e52e8a48/ol-20-06-12163-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/f3232da9dea8/ol-20-06-12163-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/8b43ff5b83db/ol-20-06-12163-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/91eddf9528f3/ol-20-06-12163-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/efb179d70b3a/ol-20-06-12163-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c6/7577082/5730a0ec30a1/ol-20-06-12163-g08.jpg

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Cytotoxic T Lymphocyte Antigen-4 Down-Regulates T Helper 1 Cells by Increasing Expression of Signal Transducer and Activator of Transcription 3 in Acute Graft-versus-Host Disease.在急性移植物抗宿主病中，细胞毒性T淋巴细胞抗原4通过增加信号转导子和转录激活子3的表达来下调辅助性T细胞1。
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Antithymocyte globulin combined with cyclosporine A down-regulates T helper 1 cells by modulating T cell immune response cDNA 7 in aplastic anemia.
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