Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity.
Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity.
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DOI：
10.1615/critrevimmunol.2016017098
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发表时间：
2016
影响因子：
1.3
通讯作者：
Griffith TS
中科院分区：
文献类型：
--
作者：
Danahy DB;Strother RK;Badovinac VP;Griffith TS
脓毒症患者经历慢性免疫抑制，导致对通常由T细胞控制的感染的易感性增强。临床研究发现脓毒症患者细胞凋亡增加，CD4和CD8 T细胞总数减少，提示免疫抑制的机制。脓毒症的实验模型，包括盲肠结扎和穿刺，逆转了这一临床观察结果，以促进假设驱动的研究，并允许使用一系列实验工具来探索脓毒症对t细胞免疫的影响。除了数量损失外，脓毒症还在功能上损害了CD4和CD8 T细胞的抗原驱动增殖能力和效应功能。败血症引起的T细胞数量和质量的损伤导致小鼠的保护能力降低，对新的或以前遇到的感染的易感性增加。因此，脓毒症的临床和实验研究已经开始阐明脓毒症对t细胞介导的免疫的影响以及潜在的t细胞内在和外在驱动慢性免疫抑制的机制。未来的工作将探索败血症对最近发现的组织驻留记忆（TRM） T细胞和树突状细胞的影响，这些细胞提供针对局部感染的强大保护，而树突状细胞则需要激活T细胞并促进有效的T细胞反应。
Septic patients experience chronic immunosuppression resulting in enhanced susceptibility to infections normally controlled by T cells. Clinical research on septic patients has shown increased apoptosis and reduced total numbers of CD4 and CD8 T cells, suggesting contributing mechanism driving immunosuppression. Experimental models of sepsis, including cecal ligation and puncture, reverse translated this clinical observation to facilitate hypothesis-driven research and allow the use of an array of experimental tools to probe the impact of sepsis on T-cell immunity. In addition to numerical loss, sepsis functionally impairs the antigen-driven proliferative capacity and effector functions of CD4 and CD8 T cells. Sepsis-induced impairments in both the quantity and quality of T cells results in reduced protective capacity and increased susceptibility of mice to new or previously encountered infections. Therefore, the combined efforts of clinical and experimental sepsis research have begun to elucidate the impact of sepsis on T-cell-mediated immunity and potential T-cell-intrinsic and -extrinsic mechanisms driving chronic immunosuppression. Future work will explore the impact of sepsis on the recently appreciated tissue-resident memory (TRM) T cells, which provide robust protection against localized infections, and dendritic cells, which are needed to activate T cells and promote effective T-cell responses.