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已发表论文
脓毒症中非常规 T 细胞的新兴作用及治疗潜力
Authors Gu S , Zhang P, Zhang C , Tang T, Chang T, Dong L, Gao W, Tang Z
Received 10 June 2025
Accepted for publication 9 September 2025
Published 20 September 2025 Volume 2025:18 Pages 13139—13157
DOI https://doi.org/10.2147/JIR.S545532
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Anh Ngo
Shuaipeng Gu,1 Peidong Zhang,1 Cong Zhang,1 Tingxuan Tang,2 Teding Chang,1 Liming Dong,1 Wei Gao,1,* Zhaohui Tang1,*
1Department of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wei Gao; Zhaohui Tang, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People’s Republic of China, Email wei-gao@tjh.tjmu.edu.cn; tangzh@tjh.tjmu.edu.cn
Abstract: Sepsis represents a dynamic, dysregulated host immune response to infection in which unconventional T cells—γδ T cells, mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and double-negative T cells—actively shape the balance between early hyperinflammation and subsequent immune paralysis across time and tissues. These cells employ unique antigen recognition mechanisms to trigger rapid immune responses. γδ T cells facilitate early pathogen elimination and immune regulation, whereas MAIT cells detect microbial metabolites and modulate the systemic inflammation. NKT cells balance immune homeostasis through dual pro- and anti-inflammatory cytokine production. This review classifies these subsets and examines their sepsis-related functions alongside immunotherapies targeting them, such as cytokine manipulation, immunomodulators, and checkpoint inhibitors. Elucidating the precise mechanisms underlying sepsis could advance therapies that restore immune equilibrium and potentially improve clinical outcomes. Future studies should unravel the interactions between unconventional T cells and broader immune networks while translating the findings into practical treatments. Understanding the dynamic roles of these cells provides pathways for tailored interventions in sepsis management.
Keywords: sepsis, γδ T cells, invariant natural killer t cells, mucosal-associated invariant t cells, double-negative t cells, immunotherapy
1Department of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wei Gao; Zhaohui Tang, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People’s Republic of China, Email wei-gao@tjh.tjmu.edu.cn; tangzh@tjh.tjmu.edu.cn
Abstract: Sepsis represents a dynamic, dysregulated host immune response to infection in which unconventional T cells—γδ T cells, mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and double-negative T cells—actively shape the balance between early hyperinflammation and subsequent immune paralysis across time and tissues. These cells employ unique antigen recognition mechanisms to trigger rapid immune responses. γδ T cells facilitate early pathogen elimination and immune regulation, whereas MAIT cells detect microbial metabolites and modulate the systemic inflammation. NKT cells balance immune homeostasis through dual pro- and anti-inflammatory cytokine production. This review classifies these subsets and examines their sepsis-related functions alongside immunotherapies targeting them, such as cytokine manipulation, immunomodulators, and checkpoint inhibitors. Elucidating the precise mechanisms underlying sepsis could advance therapies that restore immune equilibrium and potentially improve clinical outcomes. Future studies should unravel the interactions between unconventional T cells and broader immune networks while translating the findings into practical treatments. Understanding the dynamic roles of these cells provides pathways for tailored interventions in sepsis management.
Keywords: sepsis, γδ T cells, invariant natural killer t cells, mucosal-associated invariant t cells, double-negative t cells, immunotherapy