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CD4+CD45RClowTreg在大鼠肝移植免疫耐受中的调节作用研究

周林 李瀚 赵阳 汪京 贾亚男 张欣雪 李先亮 郎韧 贺强

周林, 李瀚, 赵阳, 等. CD4+CD45RClowTreg在大鼠肝移植免疫耐受中的调节作用研究[J]. 器官移植, 2021, 12(5): 579-587. doi: 10.3969/j.issn.1674-7445.2021.05.012
引用本文: 周林, 李瀚, 赵阳, 等. CD4+CD45RClowTreg在大鼠肝移植免疫耐受中的调节作用研究[J]. 器官移植, 2021, 12(5): 579-587. doi: 10.3969/j.issn.1674-7445.2021.05.012
Zhou Lin, Li Han, Zhao Yang, et al. Study of the role of CD4+CD45RClowTreg in regulating immune tolerance of rats undergoing liver transplantation[J]. ORGAN TRANSPLANTATION, 2021, 12(5): 579-587. doi: 10.3969/j.issn.1674-7445.2021.05.012
Citation: Zhou Lin, Li Han, Zhao Yang, et al. Study of the role of CD4+CD45RClowTreg in regulating immune tolerance of rats undergoing liver transplantation[J]. ORGAN TRANSPLANTATION, 2021, 12(5): 579-587. doi: 10.3969/j.issn.1674-7445.2021.05.012

CD4+CD45RClowTreg在大鼠肝移植免疫耐受中的调节作用研究

doi: 10.3969/j.issn.1674-7445.2021.05.012
基金项目: 

北京市自然科学基金 7212042

首都医科大学科研培育基金 PYZ20010

首都医科大学科研培育基金 PYZ20014

详细信息
    作者简介:

    周林,男,1987年生,博士,主治医师,研究方向为肝移植的基础与临床研究,Email:commamder_fmmu@126.com

    通讯作者:

    郎韧,男,1968年生,博士,主任医师,研究方向为肝移植与肝胆胰恶性肿瘤, E-mail: langren@bjcyh.com

    贺强,男,1964年生,博士,主任医师,研究方向为肝移植与肝胆胰恶性肿瘤, E-mail: heqiang349@sina.com

  • 中图分类号: R617, R392.4

Study of the role of CD4+CD45RClowTreg in regulating immune tolerance of rats undergoing liver transplantation

More Information
  • 摘要:   目的  探讨CD4+CD45RClow调节性T细胞(Treg)在肝移植免疫耐受诱导中的作用。  方法  建立急性排斥反应(AR)[Lewis→Brown Norway(BN),AR组]与自发耐受(BN→Lewis,耐受组)大鼠肝移植模型,每组6只。并设立假手术组(对照组),Lewis大鼠和BN大鼠各3只。对各组大鼠肝组织进行病理学检查;检测各组大鼠外周血、移植肝、脾脏T细胞亚群和浆细胞样树突状细胞(pDC)的表达情况,分析pDC与CD4+CD45RClowTreg的相关性;检测各组大鼠移植肝和脾脏CD4、CD45RC、CD103的表达情况。  结果  AR组大鼠病理学主要表现为移植肝炎症细胞浸润和组织结构紊乱。与AR组大鼠比较,耐受组大鼠外周血CD4+CD25+Treg、CD8+Treg表达水平均升高(均为P < 0.05)。外周血CD4+CD25+Treg与CD8+Treg表达水平呈正相关(r=0.742,P=0.022)。AR组大鼠外周血CD4+CD45RChighT细胞水平高于耐受组和对照组大鼠(均为P < 0.05)。与AR组大鼠比较,耐受组大鼠脾脏CD4+CD45RClowTreg表达水平升高,外周血、移植肝、脾脏CD8+CD45RClowTreg表达水平均升高(均为P < 0.05)。与对照组和AR组大鼠比较,耐受组大鼠外周血CD8+CD45RClowTreg/CD8+T比值升高,外周血、移植肝、脾脏中pDC的表达水平均升高(均为P < 0.05);且CD4+CD45RClowTreg与pDC表达水平的变化呈正相关(r=0.506,P=0.016)。耐受组大鼠移植肝和脾脏CD4、CD45RC、CD103的表达均增多;而AR组大鼠移植肝CD4、CD45RC的表达增多,CD103表达降低。  结论  CD4+CD45RClowTreg是具有负向免疫调控作用的细胞亚群,与CD8+CD45RClowTreg及pDC等构成免疫耐受诱导的调节性细胞网络。

     

  • 图  1  各组大鼠肝组织病理学染色结果(HE,×200)

    Figure  1.  Pathological staining results of liver tissues of rats in each group

    图  2  各组大鼠外周血T细胞亚群的流式细胞图

    注:A图为耐受组大鼠CD4+CD25+Treg、CD4+T细胞、CD8+T细胞的流式散点图;B图为AR组大鼠CD4+CD25+Treg、CD4+T细胞、CD8+T细胞的流式散点图;C图为对照组大鼠CD4+CD25+Treg、CD4+T细胞、CD8+T细胞的流式散点图。

    Figure  2.  Flow cytometry of T cell subsets in peripheral blood of rats in each group

    图  3  各组大鼠CD4+CD45RClowTreg、CD8+CD45RClowTreg分析结果

    注:A图为各组大鼠不同组织中CD4+CD45RClowTreg表达水平;B图为各组大鼠不同组织中CD8+CD45RClowTreg表达水平;C图为各组大鼠外周血CD4+CD45RClowTreg/CD4+T比值和CD8+CD45RClowTreg/CD8+T比值;与对照组比较,aP<0.05,与AR组比较,bP<0.05。

    Figure  3.  Analysis results of CD4+CD45RClowTreg and CD8+CD45RClowTreg of rats in each group

    图  4  各组大鼠pDC表达的差异性分析

    注:A图为各组外周血pDC的表达水平;B图为各组移植肝pDC的表达水平;C图为各组脾脏pDC的表达水平;D图为CD4+CD45RClowTreg与pDC的相关性分析;E图为各组外周血pDC流式峰值图;与对照组比较,aP<0.05,与AR组比较,bP<0.05。

    Figure  4.  Differential analysis of pDC expression of rats in each group

    图  5  各组大鼠移植肝和脾脏CD4、CD45RC、CD103的表达(免疫组化,×200)

    注:A图为各组移植肝CD4、CD45RC、CD103的染色结果;B图为各组脾脏CD4、CD45RC、CD103的染色结果。

    Figure  5.  Expression of CD4, CD45RC and CD103 in liver allograft and spleen of rats in each group

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  • 收稿日期:  2021-05-07
  • 刊出日期:  2021-09-15

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