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中华重症医学电子杂志 ›› 2021, Vol. 07 ›› Issue (01) : 48 -54. doi: 10.3877/cma.j.issn.2096-1537.2021.01.009

所属专题: 文献

综述

脓毒症T淋巴细胞亚群免疫监测的研究进展
张思也1, 侯粲2,(), 钟燕军3, 伍国宝3   
  1. 1. 410011 长沙,湖南省人民医院 湖南师范大学附属第一医院重症医学科 湖南师范大学临床医学院;410011 长沙,中南大学湘雅二医院重症监护中心
    2. 410011 长沙,中南大学湘雅二医院重症监护中心;410011 长沙,中南大学湘雅二医院代谢内分泌科 糖尿病免疫学教育部重点实验室(中南大学) 国家代谢性疾病临床医学研究中心
    3. 410011 长沙,中南大学湘雅二医院重症监护中心
  • 收稿日期:2020-08-25 出版日期:2021-02-28
  • 通信作者: 侯粲
  • 基金资助:
    国家自然科学基金青年基金(81701962,81200580)

Review on advances of monitoring T-cell subsets in septic patients

Siye Zhang1, Can Hou2,(), Yanjun Zhong3, Guobao Wu3   

  1. 1. Intensive Care Unit, Hunan Provincial People's Hospital/the First Hospital Affiliated with Hunan Normal University, the Clinical Medicine of Hunan Normal University, Changsha 410011, China; Intensive Care Unit, the Second Xiangya Hospital of Central South University, Changsha 410011, China
    2. Intensive Care Unit, the Second Xiangya Hospital of Central South University, Changsha 410011, China; Department of Metabolism & Endocrinology, the Second Xiangya Hospital, Central South University, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha 410011, China
    3. Intensive Care Unit, the Second Xiangya Hospital of Central South University, Changsha 410011, China
  • Received:2020-08-25 Published:2021-02-28
  • Corresponding author: Can Hou
引用本文:

张思也, 侯粲, 钟燕军, 伍国宝. 脓毒症T淋巴细胞亚群免疫监测的研究进展[J]. 中华重症医学电子杂志, 2021, 07(01): 48-54.

Siye Zhang, Can Hou, Yanjun Zhong, Guobao Wu. Review on advances of monitoring T-cell subsets in septic patients[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2021, 07(01): 48-54.

由于脓毒症免疫反应的异质性、复杂的信号通路、促炎与抗炎的相互作用等诸多因素影响,脓毒症疗效及预后依然欠佳。脓毒症免疫抑制增加院内感染及死亡的风险。即使存活的患者通常也会出现长期的免疫抑制状态,是远期死亡的主要原因之一。此次新型冠状病毒肺炎(COVID-19)的流行,重型及危重型患者均符合脓毒症诊断标准。通过对脓毒症,尤其是重型、危重型COVID-19患者外周血辅助T细胞、调节性T细胞和CD8+T细胞研究,发现监测其变化趋势与脓毒症不同时期的免疫激活和免疫抑制显著相关。正确评估患者的免疫状态是个体化治疗的前提。本文综述了脓毒症T淋巴细胞亚群的变化,以期为精准治疗脓毒症和改善脓毒症患者的预后提供监测指标。

Although the understanding of the pathophysiological mechanism of sepsis has significantly improved, the outcome of septic patients remains poor. It is because of the heterogeneity of immune response, complex signaling pathways, the interplay of pro-inflammatory and anti-inflammatory processes and so on. Moreover, immunosuppression in sepsis increases the risk of death. Even survivors often remain a persistent immunosuppression status, which is one of the main reasons for long-term mortality. During pandemic of coronavirus disease 2019(COVID-19), severe COVID-19 patients also meet the diagnostic criteria of sepsis. In different periods of sepsis, there are close correlations between the counts of T cell subsets and immune status, demonstrated by monitoring peripheral helper T cells, regulatory T cells and CD8+T cells. The premise of appropriate treatment is to assess the patient's immune status precisely. Therefore, this review focuses on the change of T cell subsets counts, especially in patients with COVID-19, aiming to provide a monitoring indicator for precision immune treatment and improve outcome in sepsis.

表1 T细胞亚群相关细胞因子的作用机制及意义
表2 脓毒症中CD4+T淋巴细胞亚群的变化趋势及意义
CD4+T细胞亚群 性质 生理作用 生物学功能 变化趋势 临床意义
Th1 促炎 分泌CKs,如:IL-2、IFN-γ、TNF-α 介导细胞免疫,引起迟发型超敏反应 早期:升高 早期:Th2、Th1均升高,形成促炎与抗炎同时存在的炎症激活状态[24]
中晚期:升高或与病死率有关,但近期有文献报道其脓毒症中的独立变化趋势无明显统计学差异[24]
休克期:可下降 休克期:明显下降提示免疫抑制[22]
Th2 抑炎 分泌CKs,如:IL-4、5、6、10、13 辅助体液免疫、抗寄生虫感染 早期:迅速、显著升高 早期:Th2、Th1均升高,形成促炎与抗炎同时存在的炎症激活状态
中晚期:逐渐下降或持续高水平 中晚期:持续高水平Th2往往与不良预后相关
休克期:可下降 休克期:明显下降提示免疫抑制
Th17 促炎 分泌CKs,如IL-17 抵御细胞外细菌、真菌感染以及自身免疫 早期:升高 早期:提示抗炎反应,但过度的活化会加重组织损伤
中晚期:逐渐下降或高水平 中晚期:高水平提示更高概率的不良结局[26]
休克期:下降/升高 升高表示高度活化的促炎反应而不是更好的保护作用,加重病情
Tregs 抑炎 不同细胞群作用不同,可与受体结合直接作用,也可分泌IL-10或TGF-β 限制感染性疾病组织损伤,但也可增加病原体存活概率,抑制自身免疫疾病的发生发展,控制过敏反应 早期:升高 早期:限制脓毒症早期的促炎反应[28]
中晚期:可持续存在 参与免疫抑制,持续存在可降低宿主对继发院内感染的抵抗力[30]
休克期:3天内即可升高 进一步加重免疫抑制
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