The role of regulatory T cells in immune dysfunction during sepsis

doi:10.5847/wjem.j.1920-8642.2015.01.001

Abstract

Abstract:

BACKGROUND: Although regulatory T cells (Tregs) are key to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the stage of sepsis. This article aimed to review the current literature on the role of Tregs in the pathophysiology of septic response, attempting to investigate the role of Tregs in immune dysfunction during sepsis.
DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure and PubMed. Articles on the role of Tregs in immune dysfunction during sepsis were identified.
RESULTS: The identified articles indicated that Treg levels can be used for the assessment of the course of sepsis. The inhibition of Treg activity can promote the recovery of immune function.
CONCLUSION: Since the mechanism of Tregs is complex during the sepsis, more studies are needed.

Key words: Regulatory T cells, Sepsis, Immune dysfunction

Chao Cao, Tao Ma, Yan-fen Chai, Song-tao Shou. The role of regulatory T cells in immune dysfunction during sepsis[J]. World Journal of Emergency Medicine, 2015, 6(1): 5-9.

References 30

1	Cheng B, Xie G, Yao S, Wu X, Guo Q, Gu M, et al. Epidemiology of sever sepsis in critically ill surgical patients in ten university hospitals in China. Crit Care Med 2007; 35:2538-2546.
2	Wan YY. Regulatory T cells: immune suppression and beyond. Cell Mol Immunol 2010; 7:204-210. pmid: 20383175
3	Ohkura N, Sakaguchi S. Regulatory T cells: roles of T cell receptor for their development and function. Semin Immunopathol 2010; 32:95-106.
4	Wang L, Xie Y, Zhu LJ, Chang TT, Mao YQ, Li J. An association between immunosenescence and CD4⁺CD25⁺ regulatory T cells: a systematic review. Biomed Environ Sci 2010; 23:327-332. pmid: 20934123
5	Yao YM, Huang LF. The potential role of regulatory T cells in postburn sepsis. Zhonghua Shao Shang Za Zhi 2011; 27:81-83. pmid: 21651840
6	Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol 2008; 8:523-532.
7	Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, et al. Disruption of a new forkhead/ winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 2001; 27:68-73. doi: 10.1038/83784 pmid: 11138001
8	Jane Hoyt Buckner. Mechanisms of impaired regulation by CD4⁺CD25⁺FOXP3⁺ regulatory T cells in human autoimmune diseases. Nat Rev Immunol 2010; 10:849-859. pmid: 21107346
9	Williams LM, Rudensky AY. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat lmmunol 2007; 8:277-284.
10	Wan YY, Flavell RA. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007; 445:766-770.
11	Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 2001; 27:68-73. doi: 10.1038/83784 pmid: 11138001
12	Pandey NR, Bian YY, Shou ST. Significance of blood pressure variability in patients with sepsis. World J Emerg Med 2014; 5:42-47. pmid: 25215146
13	Venet F, Pachot A, Debard AL, Bohé J, Bienvenu J, Lepape A, et al. Increased percentage of CD4⁺CD25⁺ regulatory T cells during septic shock is due to the decrease of CD4⁺CD25^- lymphocytes. Crit Care Med 2004; 32:2329-2331. doi: 10.1097/01.ccm.0000145999.42971.4b pmid: 15640650
14	Taylor AL, Llewelyn MJ. Superantigen-induced proliferation of human CD4⁺CD25^-T cells is followed by a switch to a functional regulatory phenotype. J Immunol 2010; 185:6591-6598. pmid: 21048104
15	Zou Q, Wen W, Zhang XC. Presepsin as a novel sepsis biomarker. World J Emerg Med 2014; 5:16-19. doi: 10.5847/wjem.j.issn.1920-8642.2014.01.002 pmid: 25215141
16	Wisnoski N, Chung CS, Chen Y, Huang X, Ayala A. The contribution of CD4⁺CD25⁺ T- regulatory-cells to immune suppression in sepsis. Shock 2007; 27:251-257.
17	Venet F, Pachot A, Debard AL, Bohe J, Bienvenu J, Lepape A, et al. Human CD4⁺CD25⁺ regulatory T lymphocytes inhibit lipopolysaccharide-induced monocyte survival through a Fas/Fas ligand-dependent mechanism. J Immunol 2006; 177:6540-6547.
18	Huang LF, Yao YM, Dong N, Yu Y, He LX, Sheng ZY. Association between regulatory T cell activity and sepsis and outcome of severely burned patients: a prospective, observational study. Crit Care 2010; 14 (R3). Epub 2010 Jan 11.
19	Zhang Y, Yao YM, Huang LF, Dong N, Yu Y, Sheng ZY. The potential effect and mechanism of high-mobility group box 1 protein on regulatory T cell-mediated immunosuppression. J Interferon Cytokine Res 2011; 31:249-257. pmid: 21087077
20	Hein F, Massin F, Cravoisy-Popovic A, Barraud D, Levy B, Bollaert PE, et al. The relationship between CD4⁺ CD25⁺CD127- regulatory T cells and inflammatory response and outcome during shock states. Crit Care 2010; 14:132-142.
21	Saito K, Wagatsuma T, Toyama H, Ejima Y, Hoshi K, Shibusawa M, et al. Sepsis is characterized by the increase in percentages of circulating CD4⁺CD25⁺ regulatory T cells and plasma level of soluble CD25. J Exp Med 2008; 216:61-68.
22	Heuer JG, Zhang T, Zhao J, Ding C, Cramer M, Justen KL, et al. Adopfive transfer of in vitro-stimulated CD4⁺CD25⁺ regulatory T cells increases bacterial clearance and improves survival in polymicrobial sepsis. J Immunol 2005; 174:7141-7146.
23	Murphy TJ, Choileain N, Zang Y, Mannick JA, Lederer JA. CD4⁺CD25⁺ regulatory T cells control innate immune reactivity after injury. J Immunol 2005; 174:2957-2963.
24	Scumpia PO, Delano MJ, Kelly KM, O'Malley KA, Efron PA, McAuliffe PF, et al. Increased natural CD4⁺CD25⁺ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis. J Immunol 2006; 177:7943-7949. pmid: 17114466
25	Chen X, Bäumel M, Männel DN, Howard OM, Oppenheim JJ. Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4⁺CD25⁺ T regulatory cells. J Immunol 2007; 179:154-161. pmid: 17579033
26	Venet F, Chung CS, Monneret G, Huang X, Horner B, Garber M, et al. Regulatory T cell populations in sepsis and trauma. J Leukoc Biol 2008; 83:523-535. pmid: 17913974
27	Thomas JO, Travers AA. HMG1 and 2, and related 'architectural' DNA-binding proteins. Trends Biochem Sci 2001; 26:167-174. pmid: 11246022
28	Inoue S, Bo L, Bian J, Unsinger J, Chang K, Hotchkiss RS. Dose-dependent effect of anti-CTLA-4 on survival in sepsis. Shock 2011; 36:38-44.
29	Scumpia PO, Delano MJ, Kelly-Scumpia KM, Weinstein JS, Wynn JL, Winfield RD, et al. Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis. Blood 2007; 110:3673-3681.
30	Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, et al. Increased circulating regualtroy T cells (CD4⁺CD25⁺CD127^-) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med 2009; 35:678-686. pmid: 18946659

[1]	Hui Chen, Yuanhua Lu, Songjie Bai, Yang Li, Tao Wang, Long Cai, Xinyi Yang, Yang Fang, Jianguo Wan, Yaqun Tang, Wenqiang Tao, Meiling Huang, Wei Zhong, Fen Liu, Kejian Qian. Stress-hyperglycemia ratio and glycemic variability predict severity and mortality in sepsis-associated acute respiratory distress syndrome [J]. World Journal of Emergency Medicine, 2026, 17(3): 250-257.
[2]	Zengzheng Ge, Xin Lu, Shiyuan Yu, Mubing Qin, Chao Gong, Qun Xu, Yanxia Gao, Joseph Harold Walline, Huadong Zhu, Yi Li. Diagnostic value of mismatch-negativity and P3a event-related potentials for sepsis-associated encephalopathy in non-sedated patients: a pilot study [J]. World Journal of Emergency Medicine, 2026, 17(2): 172-178.
[3]	Jinlan Ma, Li Peng, Hongming Yu, Jianfeng Xie, Ying Tang, Shenglin Su, Libing Ma, Xiaojun Yang. Single-cell transcriptomics reveals pathogen-specific monocyte heterogeneity and potential biomarkers in gram-positive versus gram-negative bloodstream infections [J]. World Journal of Emergency Medicine, 2026, 17(2): 162-171.
[4]	Yi Yao, Wenjin Li, Dejiang Hong, Ze Chen, Kai Peng, Guangju Zhao. Prediction model for quality of life in sepsis survivors one year after discharge [J]. World Journal of Emergency Medicine, 2026, 17(2): 105-112.
[5]	Xin Lu, Mubing Qin, Zengrui Song, Ying Chen, Huadong Zhu, Yanxia Gao, Yi Li. Normal initial lactate level in sepsis patients: is lactate still useful for prognosis prediction? [J]. World Journal of Emergency Medicine, 2026, 17(1): 57-64.
[6]	Yuhui Pan, Yanyan Ma, Ke Wan, Yizhou Xu, Guoxing Wang, Miaorong Xie. Endothelial cell injury: a crucial link in microcirculatory dysfunction associated with sepsis [J]. World Journal of Emergency Medicine, 2026, 17(1): 28-35.
[7]	Wei Gu, Jie Zhong, Chuanzhu Lyu, Guoqiang Zhang, Miaorong Xie, Yuefeng Ma, Wei Guo. An approach for the emergency diagnosis and treatment of sepsis-associated encephalopathy in elderly individuals: a literature review [J]. World Journal of Emergency Medicine, 2025, 16(5): 415-422.
[8]	Zesheng Wu, Fanghui Chen, Chen Xiao, Xue Zhao, Yuansheng Xu, Jinyan Fang, Yinyan Shao. Long-term cardiovascular outcomes and risk factors in adult sepsis survivors: a systematic review and meta-analysis [J]. World Journal of Emergency Medicine, 2025, 16(5): 423-430.
[9]	Qiaosheng Wang, Qiong Luo, Zhiwei Su, Yan Xu, Liangshan Peng, Yin Wen, Hongke Zeng, Hongguang Ding. Activation of the α7 nicotinic acetylcholine receptor mitigates cognitive deficits in mice with sepsis-associated encephalopathy by inhibiting microglial pyroptosis [J]. World Journal of Emergency Medicine, 2025, 16(5): 438-446.
[10]	Sen Jiang, Xiandong Liu, Tong Liu, Yi Gu, Bo An, Chunxue Wang, Dongyang Zhao, Haitao Zhang, Lunxian Tang. Performance of a novel medical artificial intelligence large language model on supporting decision-making for emergency patients with suspected sepsis [J]. World Journal of Emergency Medicine, 2025, 16(5): 447-455.
[11]	Quan Li, Yun Qu, Jinfang Xue, Hai Kang, Chuanzhu Lyu. Exploring lipid-modifying therapies for sepsis through the modulation of circulating inflammatory cytokines: a Mendelian randomization study [J]. World Journal of Emergency Medicine, 2025, 16(3): 256-261.
[12]	Peili Chen, Yan Ge, Huiqiu Sheng, Wenwu Sun, Jiahui Wang, Li Ma, Enqiang Mao. The role of early changes in routine coagulation tests in predicting the occurrence and prognosis of sepsis [J]. World Journal of Emergency Medicine, 2025, 16(2): 136-143.
[13]	Chunxue Wang, Dianyin Yang, Yuxin Zhu, Qian Yang, Tong Liu, Xiandong Liu, Dongyang Zhao, Xiaowei Bao, Tiancao Dong, Li Shao, Lunxian Tang. Circulating circular RNAs act as potential novel biomarkers for sepsis secondary to pneumonia: a prospective cohort study [J]. World Journal of Emergency Medicine, 2025, 16(2): 144-152.
[14]	Azzah S Alharbi, Raghad Hassan Sanyi, Esam I Azhar. Bacteria and host: what does this mean for sepsis bottleneck? [J]. World Journal of Emergency Medicine, 2025, 16(1): 10-17.
[15]	Chao Gong, Shengyong Xu, Youlong Pan, Shigong Guo, Joseph Harold Walline, Xue Wang, Xin Lu, Shiyuan Yu, Mubing Qin, Huadong Zhu, Yanxia Gao, Yi Li. Effects of probiotic treatment on the prognosis of patients with sepsis: a systematic review [J]. World Journal of Emergency Medicine, 2025, 16(1): 18-27.

The role of regulatory T cells in immune dysfunction during sepsis Open Access

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 30

Related Articles 15

Recommended Articles

Comments