常用免疫抑制剂对Tfr细胞和Breg细胞的作用研究

于涛; 陈文; 刘志佳; 黄海燕; 肖漓; 石炳毅

doi:10.3969/j.issn.1674-7445.2018.05.007

常用免疫抑制剂对Tfr细胞和Breg细胞的作用研究

doi: 10.3969/j.issn.1674-7445.2018.05.007

100091 北京，解放军第 309 医院全军器官移植研究所器官移植与免疫调节北京市重点实验室(BZ0106) 国家卫生健康委员会肾脏移植质量控制中心

基金项目:

国家自然科学基金 81571555

国家自然科学基金 81370578

国家自然科学基金 81570680

详细信息

作者简介:
于涛，男，1978年生，硕士，主治医师，研究方向为器官移植与免疫耐受，Email：yutao309@sina.cn

通讯作者:
石炳毅，男，1951年生，硕士，主任医师，博士研究生导师，研究方向为器官移植与免疫耐受，Email：shibingyi666@126.com

中图分类号: R617, R392.4
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出版历程
- 收稿日期: 2018-07-24
- 网络出版日期: 2021-01-19
- 刊出日期: 2018-09-15

Effect of common immunosuppressants on Tfr cells and Breg cells

Organ Transplant Institute of the 309^th Hospital of People's Liberation Army, Beijing Key Laboratory of Organ Transplantation and Immunology Regulatory, Quality Control Center for Renal Transplantation of National Health Commission of the People’s Republic of China, Beijing 100091, China

More Information

Corresponding author: Shi Bingyi, Email: shibingyi666@126.com

摘要

摘要: 目的探讨常用免疫抑制剂对滤泡调节性T细胞(Tfr细胞)和调节性B细胞(Breg细胞)的作用。方法收集6例健康志愿者的外周血(每例5 mL), 采用人淋巴细胞分离液分离出淋巴细胞进行培养, 将细胞分为对照组(未加入免疫抑制剂)、环孢素组(250 ng/mL)、他克莫司组(10 ng/mL)和西罗莫司组(10 ng/mL), 分别用相应免疫抑制剂刺激48 h。用流式细胞仪检测各组淋巴细胞中Breg细胞和Tfr细胞的比例; 采用酶联免疫吸附试验(ELISA)检测各组上清液中白细胞介素(IL)-21的含量。结果与对照组比较, 环孢素组、他克莫司组和西罗莫司组淋巴细胞中Breg细胞的比例均升高, 差异均有统计学意义(均为P < 0.05);环孢素组和他克莫司组淋巴细胞中Tfr细胞比例均升高, 差异均有统计学意义(均为P < 0.05);西罗莫司组淋巴细胞中Tfr细胞比例下降, 差异亦有统计学意义(P < 0.05)。ELISA检测结果显示, 与对照组比较, 环孢素组和他克莫司组上清液中IL-21含量均下降, 差异均有统计学意义(均为P < 0.05);西罗莫司对IL-21分泌的影响不大, 差异无统计学意义(P > 0.05)。结论环孢素和他克莫司具有抑制B细胞免疫反应的作用。
- 器官移植 /
- 调节性B细胞(Breg细胞) /
- 滤泡调节性T细胞(Tfr细胞) /
- 免疫抑制剂 /
- 环孢素 /
- 他克莫司 /
- 西罗莫司 /
- 白细胞介素(IL)-21
Abstract: Objective To investigate the effect of common immunosuppressants on the follicular regulatory T cells (Tfr cells) and regulatory B cells (Breg cells). Methods Peripheral blood samples were collected from 6 healthy volunteers (5 mL per case).The lymphocytes were isolated by human lymphocyte isolation solution and cultured.The cells were divided into the control group (without supplement of immunosuppressants), ciclosporin group (250 ng/mL), tacrolimus group (10 ng/mL) and sirolimus group (10 ng/mL).The cells were stimulated with corresponding immunosuppressants for 48 h, respectively.The proportion of Breg and Tfr cells in the lymphocytes in each group was detected by flow cytometry.The content of interleukin (IL)-21 in the supernatants of each group was detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group, the proportion of Breg cells in the lymphocytes in the ciclosporin, tacrolimus and sirolimus groups was all significantly increased (all P < 0.05).In the ciclosporin group and tacrolimus group, the proportion of Tfr cells in the lymphocytes was both significantly elevated (both P < 0.05), whereas the proportion of Tfr cells in the lymphocytes in the sirolimus group was significantly decreased (P < 0.05).ELISA demonstrated that compared with the control group, the IL-21 content in the supernatants in the ciclosporin and tacrolimus groups was both significantly decreased (both P < 0.05).Use of sirolimus exerted no significant effect upon the secretion of IL-21 (P > 0.05). Conclusions Ciclosporin and tacrolimus can inhibit the immune response of B cells.
- Organ transplantation /
- Regulatory B cell (Breg cell) /
- Follicular regulatory T cell (Tfr cell) /
- Immunosuppressant /
- Ciclosporin /
- Tacrolimus /
- Sirolimus /
- Interleukin (IL)-21

HTML全文

图 1 各组细胞中Breg细胞比例的比较

与对照组比较，^aP<0.05

Figure 1. Comparison of the proportion of Breg cells among different groups

下载: 全尺寸图片幻灯片

图 2 各组细胞中Tfr细胞比例的比较

与对照组比较, ^aP < 0.05

Figure 2. Comparison of the proportion of Tfr cells among different groups

下载: 全尺寸图片幻灯片

图 3 各组上清液中IL-21含量的比较

与对照组比较, ^aP < 0.05

Figure 3. Comparison of the content of IL-21 in the supernatants among different groups

下载: 全尺寸图片幻灯片

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