Research update on T cell immune dysfunction in sepsis and related treatments

doi:10.3877/cma.j.issn.2096-1537.2020.04.016

Abstract

Abstract:

Immune dysfunction contributes to the development of sepsis and the high mortality of sepsis. Both innate and adaptive immune system has changed during sepsis. Nonetheless, the adaptive immune dysfunction induced by T cells plays a crucial role in the late phase of sepsis. The apoptosis, exhaustion and malfunction of T cells contributes to immune-suppressive status, which leads to high risk for death from sepsis. The review focuses on the immune status and function in the early and late phase of sepsis and states the pathophysiological mechanism of adaptive immune dysfunction in sepsis, including T cell apoptosis, T cell exhaustion and dysfunction of regulatory T cells. Further, it introduces the up-to-date T cells immune therapeutics to better understand the immune dysfunction mechanism during the development of sepsis and to pursue the new target of immune therapy.

Key words: Sepsis, T cell dysfunction, Immune therapeutics

Yini Sun, Xiaochun Ma. Research update on T cell immune dysfunction in sepsis and related treatments[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2020, 06(04): 448-452.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2020.04.016

https://icu.cma-cmc.com.cn/EN/Y2020/V06/I04/448

References 41

1	Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [J]. JAMA, 2016, 315(8): 801-810.
2	Seymour CW, Kennedy JN, Wang S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis [J]. JAMA, 2019, 321(20): 2003-2017.
3	Kahn JM, Le T, Angus DC, et al. The epidemiology of chronic critical illness in the United States [J]. Crit Care Med, 2015, 43(2): 282-287.
4	Opal SM. Immunologic alterations and the pathogenesis of organ failure in the ICU [J]. Semin Respir Crit Care Med, 2011, 32(5): 569-580.
5	Cohen J, Opal S, Calandra T. Sepsis studies need new direction [J]. Lancet Infect Dis, 2012, 12(7): 503-505.
6	Angus DC. The search for effective therapy for sepsis: back to the drawing board? [J]. JAMA, 2011, 306(23): 2614-2615.
7	Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process [J]. Chest, 1997, 112(1): 235-243.
8	Boomer JS, To K, Chang KC, et al. Immunosuppression in patients who die of sepsis and multiple organ failure [J]. JAMA, 2011, 306(23): 2594-2605.
9	Delano MJ, Ward PA. Sepsis-induced immune dysfunction: can immune therapies reduce mortality? [J]. J Clin Invest, 2016, 126(1): 23-31.
10	Wang H, Zhu S, Zhou R, et al. Therapeutic potential of HMGB1-targeting agents in sepsis [J]. Expert Rev Mol Med, 2008, 10: e32.
11	Boomer JS, Green JM, Hotchkiss RS. The changing immune system in sepsis: is individualized immuno-modulatory therapy the answer? [J]. Virulence, 2014, 5(1): 45-56.
12	Beura LK, Hamilton SE, Bi K, et al. Normalizing the environment recapitulates adult human immune traits in laboratory mice [J]. Nature, 2016, 532(7600): 512-516.
13	Xie J, Chen CW, Sun Y, et al. Increased attrition of memory T cells during sepsis requires 2B4 [J]. JCI Insight, 2019, 4(9): e126030.
14	Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine [J]. Immunol Rev, 2008, 226: 205-218.
15	Tatura R, Zeschnigk M, Hansen W, et al. Relevance of Foxp3⁺ regulatory T cells for early and late phases of murine sepsis [J]. Immunology, 2015, 146(1): 144-156.
16	Boomer JS, Shuherk-Shaffer J, Hotchkiss RS, et al. A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis [J]. Crit Care, 2012, 16(3): R112.
17	Felmet KA, Hall MW, Clark RS, et al. Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure [J]. J Immunol, 2005, 174(6): 3765-3772.
18	Toti P, De Felice C, Occhini R, et al. Spleen depletion in neonatal sepsis and chorioamnionitis [J]. AMER J Clin Pathol, 2004, 122(5): 765-771.
19	Chang KC, Unsinger J, Davis CG, et al. Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis [J]. FASEB J, 2007, 21(3): 708-719.
20	Leng FY, Liu JL, Liu ZJ, et al. Increased proportion of CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells during early-stage sepsis in ICU patients [J]. J Microbiol Immunol Infect, 2013, 46(5): 338-344.
21	Venet F, Chung CS, Kherouf H, et al. Increased circulating regulatory T cells (CD4⁺ CD25⁺ CD127^-) contribute to lymphocyte anergy in septic shock patients [J]. Intensive Care Med, 2009, 35(4): 678-686.
22	Venet F, Chung CS, Monneret G, et al. Regulatory T cell populations in sepsis and trauma [J]. J Leukoc Biol, 2008, 83(3): 523-535.
23	Delano MJ, Scumpia PO, Weinstein JS, et al. MyD88-dependent expansion of an immature GR-1⁺CD11b⁺ population induces T cell suppression and Th2 polarization in sepsis [J]. J Exp Med, 2007, 204(6): 1463-1474.
24	Barnstorf I, Borsa M, Baumann N, et al. Chronic virus infection compromises memory bystander T cell function in an IL-6/STAT1-dependent manner [J]. J Exp Med, 2019, 216(3): 571-586.
25	Regis G, Icardi L, Conti L, et al. IL-6, but not IFN-gamma, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing [J]. Leukemia, 2009, 23(11): 2102-2108.
26	Jimbo A, Fujita E, Kouroku Y, et al. ER stress induces caspase-8 activation, stimulating cytochrome c release and caspase-9 activation [J]. Exp Cell Res, 2003, 283(2): 156-166.
27	Yi JS, Cox MA, Zajac AJ. T-cell exhaustion: characteristics, causes and conversion [J]. Immunology, 2010, 129(4): 474-481.
28	Hein F, Massin F, Cravoisy-Popovic A, et al. The relationship between CD4⁺CD25⁺CD127- regulatory T cells and inflammatory response and outcome during shock states [J]. Crit Care, 2010, 14(1): R19.
29	Scumpia PO, Delano MJ, Kelly KM, et al. Increased natural CD4⁺CD25⁺ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis [J]. J Immunol, 2006, 177(11): 7943-7949.
30	Kuhlhorn F, Rath M, Schmoeckel K, et al. Foxp3⁺ regulatory T cells are required for recovery from severe sepsis [J]. PLoS One, 2013, 8(5): e65109.
31	Angus DC, van der Poll T. Severe sepsis and septic shock [J]. N Engl J Med, 2013, 369(9): 840-851.
32	Efron PA, Mohr AM, Moore FA, et al. The future of murine sepsis and trauma research models [J]. J Leukoc Biol, 2015, 98(6): 945-952.
33	Lewis AJ, Rosengart MR. Bench-to-bedside: a translational perspective on murine models of sepsis [J]. Surg Infect (Larchmt), 2018, 19(2): 137-141.
34	Hotchkiss RS, Moldawer LL. Parallels between cancer and infectious disease [J]. N Engl J Med, 2014, 371(4): 380-383.
35	Brahmamdam P, Inoue S, Unsinger J, et al. Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis [J]. J Leukoc Biol, 2010, 88(2): 233-240.
36	Patera AC, Drewry AM, Chang K, et al. Frontline science: defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1 [J]. J Leukoc Biol, 2016, 100(6): 1239-1254.
37	Chang KC, Burnham CA, Compton SM, et al. Blockade of the negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis [J]. Crit Care, 2013, 17(3): R85.
38	Nalos M, Santner-Nanan B, Parnell G, et al. Immune effects of inter-feron gamma in persistent staphylococcal sepsis [J]. Am J Respir Crit Care Med, 2012, 185(1): 110-112.
39	Perales MA, Goldberg JD, Yuan J, et al. Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation [J]. Blood, 2012, 120(24): 4882-4891.
40	Unsinger J, McGlynn M, Kasten KR, et al. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis [J]. J Immunol, 2010, 184(7): 3768-3779.
41	Wesche-Soldato DE, Swan RZ, Chung CS, et al. The apoptotic pathway as a therapeutic target in sepsis [J]. Curr Drug Targets, 2007, 8(4): 493-500.

[1]	Yuanyuan Han, Sabeiti Reziya, Zhijie Mao, Aierken Mufunayi, Chen Lu, Xiaohong Sang, Mulati Aerman, Li Zhang. Effect of combined blood purification on serum inflammatory cytokines levels and clinical prognosis in patients with sepsis [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(04): 272-278.
[2]	Jianbiao Meng, Geng Zhang, Yanna Jiao. Exploratory study on early intestinal microecological changes in patients with sepsis-induced myocardial dysfunction [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(04): 279-285.
[3]	Yu Chen, Fang Feng, Lu Zhang, Jian Liu. Bioinformatics analysis to screen key pathogenic genes in septic cardiomyopathy [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(04): 286-291.
[4]	Xiaoyan Zhang, Dongqiong Xiao, Hu Gao, Lin Chen, Fajuan Tang, Xihong Li. The protective effect and mechanism of overexpression of transcription factor 12 on the cerebral cortex of rats with sepsis-associated encephalopathy [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 540-549.
[5]	Xu Wei, Ge Zhang, Jinlin Wu. Monitoring and treatment of neonatal sepsis-induced coagulopathy [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 379-386.
[6]	Xiaodan Wang, Yuan Wang, Xiangyu Cui, Xiaolei Ren. Analysis of pathogenic bacteria resistance of drug and high risk factors of death in urogenic sepsis after endoscopic surgery for upper urinary tract stones [J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(06): 611-615.
[7]	Xuecheng Wu, Yuanwei Li, Wuxiong Yuan, Jiansong Wang, Yongzhong Shi, Qiang Lu, Zhuo Li, Jia Chen, Zhe Liu, Yili Teng, Zhiyong Gao. Diagnostic value of inflammatory mediators profile combined with procalcitonin in urogenic sepsis [J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(05): 476-480.
[8]	Shangwen Dou, Huan Deng, Bangfeng Liu, Gaoyuanzhi Yue, Huacai Zhu, Yongda Liu. Role of preoperative urine culture re-examination in the prediction of infectious complications related to mini-percutaneous nephrolithotomy [J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(04): 361-366.
[9]	Ruanxin Miao, Xi Qiao. Role of Toll-like receptor in sepsis-induced acute kidney injury [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(04): 210-214.
[10]	Shiming Li, Wei Huang, Ling Liu. Mechanism of high mobility group box protein 1 mediated sepsis-induced coagulopathy and treatment progress [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(03): 269-273.
[11]	Chao Gao, Jie Chao, Haibo Qiu. Emerging roles of transcription factor T-bet of Th17 in immune imbalance of sepsis [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(03): 280-285.
[12]	Xiang Yang, Lanqi Guo, Jianfeng Xie, Haibo Qiu. Role of metagenomics next-generation sequencing in the pathogen diagnosis in sepsis [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(03): 292-297.
[13]	Jiyun Hu, Shucai Xie, Lina Zhang. Advancement of S100 calcium binding protein B in neurocritical care field [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(03): 298-303.
[14]	Rui Tan, Jing Wang, Jiangquan Yu, Ruiqiang Zheng. Progress in understanding of role of high density lipoprotein, apolipoprotein A-I, and serum amyloid A in sepsis [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(06): 749-753.
[15]	Xing Cai, Ruiqiang Zheng. Progress in application of heparin-binding protein in sepsis [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(04): 487-490.

Please choose a citation manager

Content to export