{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:55:57Z","timestamp":1790603757677,"version":"4.1.0"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20231236"],"award-info":[{"award-number":["BK20231236"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sepsis is a life-threatening syndrome of multi-organ dysfunction caused by a dysregulated host response to infection. Despite advances in supportive care, the underlying immunopathological mechanisms remain incompletely understood. A hallmark of sepsis is immunoparalysis, characterized by an early hyperinflammatory phase followed by sustained immunosuppression, predisposing patients to secondary infections and adverse outcomes. A central feature of this process is profound lymphopenia accompanied by impaired T-cell effector function. This review synthesizes current evidence on T-cell perturbations during sepsis, encompassing numerical depletion, persistent upregulation of inhibitory immune checkpoints, and dysregulated cytokine signaling. We further highlight emerging evidence on four major modes of T-cell loss and dysfunction: apoptosis, autophagy dysfunction, pyroptosis, and ferroptosis, and discuss their integrated impact on immune competence. A deeper understanding of the mechanisms underlying T-cell death may facilitate the development of targeted immunomodulatory strategies and adjunctive therapies for sepsis, an area where effective interventions remain limited.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1857308","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:04:50Z","timestamp":1790600690000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["T-cell dysfunction and death in sepsis: a mechanistic review"],"prefix":"10.3389","volume":"17","author":[{"given":"Shiyao","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Clinical Medicine and Laboratory Medicine, Jiangsu University","place":["Zhenjiang, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Clinical Medicine and Laboratory Medicine, Jiangsu University","place":["Zhenjiang, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixiang","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Clinical Medicine and Laboratory Medicine, Jiangsu University","place":["Zhenjiang, Jiangsu, China"]},{"name":"Key Laboratory of Novel Technologies for Precision Cancer Diagnosis and Treatment of Huai\u2019an City, Affiliated Hospital of Kangda College, Nanjing Medical University","place":["Lianshui, Jiangsu, China"]},{"name":"Institute of Medical Genetics and Reproductive Immunity, The Digestive and Reproductive System Cancers Precise Prevention Engineering Research Center of Jiangsu Province, School of Medical Science and Laboratory Medicine, Jiangsu College of Nursing","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B2","volume-title":"An assessment of sepsis in the United States and its burden on hospital care","year":"2024"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/ccm.0000000000004224","article-title":"Sepsis among Medicare beneficiaries: 1. 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