脓毒症中T细胞亚群变化诱导的免疫抑制

张萌; 杨正飞

doi:10.13201/j.issn.1009-5918.2024.03.011

脓毒症中T细胞亚群变化诱导的免疫抑制

张萌¹,
杨正飞^1, ,

- 中山大学孙逸仙纪念医院急诊科(广州，510120)
基金项目:
广东省自然科学基金(No：2021A1515011433)；广州市科技局基础与应用基础研究项目(No：202201010856)

详细信息

通讯作者: 杨正飞，E-mail：yangzhengfei@vip.163.com

中图分类号: R364.7

收稿日期: 2023-10-09

刊出日期: 2024-03-10

Immunosuppression induced by changes of T lymphocytes subsets in sepsis

ZHANG Meng¹,
YANG Zhengfei^1, ,

- Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

More Information

Corresponding author: YANG Zhengfei, E-mail: yangzhengfei@vip.163.com

Received Date: 09 October 2023

Publish Date: 10 March 2024

摘要

摘要: 脓毒症是由创伤、感染等引起的临床急危重综合征，其患病率和死亡率在全球范围内居高不下。随着对脓毒症病理生理机制研究的深入，免疫调节逐渐成为该领域研究热点，而T淋巴细胞是机体免疫状态的关键特征指标，其功能受损和数量锐减是导致脓毒症患者后期免疫麻痹甚至死亡的重要因素。本文综述了CD8⁺、CD4⁺及调节性T细胞在脓毒症中的变化情况和致病机制，同时分析了各类T细胞抑制性免疫检查点在脓毒症中的分子作用机制，最后阐述了脓毒症免疫治疗的相关研究进展，以期为脓毒症临床监测和治疗提供新的研究靶点和思路。
- 脓毒症 /
- 免疫抑制 /
- T淋巴细胞 /
- 抑制性免疫检查点 /
- 免疫治疗
Abstract: Sepsis is a clinical acute and critical syndrome resulting from trauma, infection, etc., and its morbidity and mortality rates are still high worldwide. Further studies on the pathophysiology of sepsis indicate that immunoregulation is a research hotspot. T lymphocytes are the key indicator of immune status, and the function impairment and depletion of T cells are important cause of immune paralysis and even death for sepsis patients at later stage. In this review, we summarized the changes and pathogenic mechanisms of CD8⁺, CD4⁺and regulatory T cells in sepsis, we meanwhile analyzed the molecular mechanism of various inhibitory immune checkpoints in sepsis. The relevant research progress of immunotherapy in sepsis was also reviewed. We hope this article can provide new research targets and ideas for clinical monitoring and treatment of sepsis.
- sepsis /
- immunosuppression /
- T lymphocytes /
- inhibitory immune checkpoint /
- immunotherapy

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图 1 Treg细胞在脓毒症中的免疫抑制机制

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表 1 CD4⁺辅助T细胞与脓毒症免疫抑制

T细胞亚群	与脓毒症相关的生理功能	脓毒症引起的免疫抑制
CD4⁺辅助T细胞^{[17, 30-32, 35-36]}
Th1	分泌INF-γ、IL-2、TNF-α；促进Tc细胞增殖、分化和成熟；促进巨噬细胞吞噬作用；加强NK细胞杀伤能力；抑制Th2分化	Th2分化增加，分泌炎症抑制因子诱导免疫抑制；Th2/Th1比例增加，且比例失衡程度与脓毒症预后显著相关
Th2	分泌IL-4，IL-5、IL-6、IL-10、IL-13；促进B细胞增殖分化为浆细胞并产生抗体；抑制Th1细胞分化。	与脓毒症急性肠屏障损伤有关
Th9	分泌IL-9、IL-10
Th17	分泌IL-17A、IL-17F、IL-21、IL22；促进嗜中性粒细胞募集和激活，并趋化其至感染部位	SIRS主导期显著上升，CARS主导期显著下降；与Treg相互制；Treg/Th17比例失衡提示免疫抑制
Th22	分泌IL-22	脓毒症急性肺损伤患者外周血中Th22比例显著上升
Tfh	分泌IL-21；促进B细胞存活、增殖和成熟；促进生发中心发育	脓毒症患者Tfh细胞显著降低；Tfh细胞与B细胞数量正相关
CD8⁺细胞毒性T细胞^{[12, 17]}	特异性识别内源pMHC-1复合物后激活；分泌穿孔素/颗粒酶等直接杀伤靶细胞，或表达INF-γ和TNF-α诱导靶细胞凋亡	凋亡增加，增值能力减弱，CD8⁺T趋于耗竭；分泌细胞因子能力减弱；恢复后的CD8⁺T免疫响应能力下降

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表 2 常见的抑制性免疫检查点

抑制性免疫检查点	配体	生理作用
CTLA-4^[38]	CD80/CD86	抑制T细胞活化
TIGIT^[42]	CD155/CD112	抑制T细胞活化
LAG-3^[44]	MHC-Ⅱ	抑制T细胞活化，促进T细胞衰竭，抑制促炎因子分泌
PD-1^[45]	PD-L1/PD-L2	抑制T细胞增殖，调控T细胞炎症因子分泌
TIM-3^[46]	Galectin-9/HMGB1	抑制T细胞增殖，诱导T细胞凋亡
BTLA^[47]	HVEM	促进T细胞凋亡

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