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学科主题: 内科学
题名:
肝移植患者Th17细胞、调节性T细胞及T淋巴细胞上PD-1分子表达的特征及意义
作者: 王英
答辩日期: 2014-05-14
导师: 施明
专业: 内科学
授予单位: 北京大学
授予地点: 北京大学解放军302医院教学医院
学位: 硕士
关键词: 肝移植 ; 急性排斥反应 ; T淋巴细胞 ; Th17细胞 ; 调节性T细胞 ; 间充质干细胞
其他题名: Characteristics of Th17 cells, regulatory T cells and PD-1 molecular expressions on T cells in liver transplant recipients
分类号: R657.3
摘要: 目的 观察肝移植患者术后Th17细胞、CD4+ CD25+FoxP3+调节性T细胞(Tregs)的特征及T淋巴细胞上PD-1分子的表达特点,探讨其在肝移植术后免疫耐受和急性排斥中的作用及临床意义,同时观察急性排斥患者应用间充质干细胞 (MSCs) 治疗后Tregs和Th17细胞的变化特点。 方法 入组肝移植患者,术后发生急性排斥反应者为急排组,未发生急性排斥反应者为非急排组,检测两组患者外周血中Th17细胞、Tregs、Tregs上功能性分子(CTLA-4、HLA-DR、Ki67、IL-10)及T淋巴细胞上PD-1分子的表达特征,并分析其与肝功指标及排斥反应活动指数(RAI)的相关性。同时对部分移植患者进行随访研究,随访点包括术前及术后1-12月。此外,还进一步观察肝移植术后发生急性排斥反应患者肝组织中Th17细胞及Tregs的特点及与RAI相关性。对部分肝移植急性排斥反应患者采用MSCs治疗,探讨患者治疗前后Th17细胞、Tregs、Tregs和CD4+T细胞上HLA-DR分子表达水平的变化。 结果 急排组患者外周血中Tregs频率、Tregs/Th17细胞比值、Tregs上功能性分子(CTLA-4、HLA-DR、Ki67、IL-10)、T淋巴细胞上PD-1分子的表达水平都显著低于非急排组,而Th17细胞频率及IL-17+INF-γ+T细胞在急排组中则明显增高。急排组患者外周血中Th17细胞频率、Tregs频率、Tregs/Th17细胞比值、T淋巴细胞上PD-1分子的表达水平与肝功指标呈明显相关性。肝组织内Tregs及Th17细胞数量都随排斥反应加重而增加,而Tregs/Th17细胞比值与RAI呈负性相关。在随访研究中发现,当患者发生急性排斥反应时,外周血中Tregs频率降低,而Th17细胞频率升高。急性排斥反应消失后,各项免疫指标恢复较平稳状态。经MSCs治疗后,急性排斥患者外周血中Tregs频率明显升高,而Th17细胞频率变化不明显,且CD4+T细胞活化能力降低,但Tregs上HLA-DR分子表达水平无显著性差异。 结论 Th17细胞、Tregs及Tregs上功能性分子(CTLA-4、HLA-DR、Ki67、IL-10)以及T淋巴细胞上PD-1分子变化可能与肝移植患者产生急性排斥反应有关。应用MSCs治疗,肝移植急性排斥患者临床症状好转,且可能通过增加外周血中Tregs的数量及抑制CD4+T细胞的活化控制急性排斥反应,为肝移植患者急性排斥反应治疗提供新思路。
英文摘要: Objective: To investigate the characteristics of Th17 cells, regulatory T cells (Tregs) and PD-1 molecular expressions on T cells in liver transplant recipients, and its association with clinical parameters. In addition, the characteristics of Th17 cells, Tregs in peripheral blood from acute rejection patients with mesenchymal stem cells (MSCs) transfusion were demonstrated. Methods: Liver allograft recipients were enrolled in present study, and divided into acute rejection group and non acute rejection group. Then the characteristics of Th17 cells, Tregs, and the functional molecules of CTLA-4, HLA-DR, Ki67 and IL-10 expressions on Tregs, and PD-1 molecule expressions on T cells in all the patients were measured; in addition, their correlations with liver function index and rejection activity index (RAI) were also analysed. Some enrolled patients were follow-up for one year with longitudinal study. Furthermore, the characteristics of Th17 cells, Tregs in liver biopsy samples from acute rejection patients were tested. Nine enrolled patients with acute rejection were treated with MSCs, and the characteristics of Th17 cells, Tregs, HLA-DR molecules expressions on CD4+T cells and Tregs in these patients were analyzed. Results: The frequency of Tregs, Tregs/Th17 cells ratio, and the function molecules expressions on Tregs and the PD-1 molecule expressions on T cells in non acute rejection group were significantly higher than those in acute rejection group, while the frequencies of Th17 cells and IL-17+INF-γ+T cells were higher in acute rejection group than those in non acute rejection group. There were significant correlations between frequencies of Tregs and Th17 cells, Tregs/Th17 cells ratio, PD-1 molecule expressions on T cells and liver function index. The numbers of Tregs and Th17 cells infiltrating allograft were up-regulated with the aggravation of acute rejection, but Tregs/Th17 cells ratio was negatively correlated with RAI. The longitudinal analysis revealed that the frequency of circulating Th17 cells was dramatically increased at the onset of acute rejection, while the frequency of circulating Tregs was significantly decreased. After MSCs treatment, the the frequency of circulating Tregs was significantly increased, whilst the frequency of circulating Th17 cells was shown not significant difference. Conclusions: Th17 cells, Tregs, and PD-1 molecule expression on T cells may be involved in alloreactive response in liver transplant recipients. MSCs treatment could alleviate alloreactive response by up-regulation of Tregs and suppression the activity of CD4+T cells.
语种: 中文
出处: http://xuewei.bjmu.edu.cn/simpsearch.action?keyword=肝移植患者Th17细胞、调节性T细胞及T淋巴细胞上PD-1分子表达的特征及意义&dbid=72
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/105428
Appears in Collections:北京大学解放军302医院教学医院_学位论文

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作者单位: 北京大学解放军302医院教学医院

Recommended Citation:
王英. 肝移植患者Th17细胞、调节性T细胞及T淋巴细胞上PD-1分子表达的特征及意义[D]. 北京大学解放军302医院教学医院. 北京大学. 2014.
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