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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。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.
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Key words:
- sepsis /
- immunosuppression /
- T lymphocytes /
- inhibitory immune checkpoint /
- immunotherapy
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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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