ArticleCritical care (London, England)2012
A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis.
Article in Critical care (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 3 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
143 citing papers in PubMed, 3 syntheses or guidelines pooled it, 242 citations in OpenAlex.
- Inhibitory Immune Checkpoint Molecule Expression in Clinical Sepsis Studies: A Systematic Review.Critical care medicine · 2020Pooled it
- The immunosuppressive face of sepsis early on intensive care unit-A large-scale microarray meta-analysis.PloS one · 2018Pooled it
- Endogenous IgG hypogammaglobulinaemia in critically ill adults with sepsis: systematic review and meta-analysis.Intensive care medicine · 2015Pooled it
- Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial.Critical care medicine · 2022Trial
- T Cell- and Monocyte-Specific RNA-Sequencing Analysis in Septic and Nonseptic Critically Ill Patients and in Patients with Cancer.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Persistent lymphopaenia in critically ill patients with and without sepsis: An Australian and New Zealand point prevalence study.Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2026Article
- Factors associated withJournal of thoracic disease · 2026Article
- Neurocognitive Aging Following Acute Illness: Pathobiology and a Framework for Developing Neurotherapeutic Agents.Brain and behavior · 2026Review
- Pathogen-specific host responses define distinct pneumonia endotypes in the human lung.bioRxiv : the preprint server for biology · 2026Article
- TIM-3, a potential target for sepsis therapy.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Review
- Cytokine-mediated, organ-specific immune modulation and dysregulation of innate lymphocytes in sepsis.Seminars in immunopathology · 2026Review
- Sepsis induces long-term reprogramming of human HSPCs and drives myeloid dysregulation in sepsis survivors.Journal of inflammation (London, England) · 2026Article
- Failure of early lymphocyte recovery identifies sepsis patients with initial lymphopenia at highest risk for late mortality.PloS one · 2026Article
- Admission CD4Frontiers in cellular and infection microbiology · 2026Observational
- Impact of baseline lymphopenia on prognosis of patients with septic shock.BMC infectious diseases · 2025Article
- The Role and Research Progress of CD8Biomedicines · 2025Review
- Peri-Operative Antimicrobial Prophylaxis Modulates CD4Antibiotics (Basel, Switzerland) · 2025Article
- Dynamic alterations of lymphocyte subsets following sepsis in octogenarian and elder patients.Journal of intensive medicine · 2025Article
- T Cell Exhaustion and Function State Correlated With Outcomes in Patients With Intra-Abdominal Candidiasis.Mycoses · 2025Article
- Lower Plasma IL-32 Levels Linked to Better Survival in Sepsis.Biomedicines · 2025Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
introductionSevere sepsis is characterized by an initial hyper-inflammatory response that may progress to an immune-suppressed state associated with increased susceptibility to nosocomial infection. Analysis of samples obtained from patients who died of sepsis has identified expression of specific inhibitory receptors expressed on lymphocytes that are associated with cell exhaustion. The objective of this study was to prospectively determine the pattern of expression of these receptors and immune cell function in patients with acute sepsis.
methodsTwenty-four patients with severe sepsis were enrolled within 24 hours of the onset of sepsis, as were 12 age-matched healthy controls. Peripheral blood was obtained at enrollment and again seven days later. Immune cell subsets and receptor expression were extensively characterized by quantitative flow cytometry. Lymphocyte function was assayed by stimulated cytokine secretion and proliferation assays. Results were also correlated to clinical outcome.
resultsAt the onset of severe sepsis, patients had decreased circulating innate and adaptive immune cells and elevated lymphocyte expression of receptors associated with cell activation compared to controls. Samples analyzed seven days later demonstrated increased expression of the inhibitory receptors CTLA4, TIM-3 and LAG-3 on T lymphocytes accompanied by decreased expression of the IL-7 receptor. Functional assays revealed impaired secretion of interferon γ following stimulation in vitro, which was reversible by incubation overnight in fresh media. Impaired secretion of IFNγ correlated with death or development of secondary infection.
conclusionsLymphocytes from patients with acute sepsis upregulate expression of receptors associated with cell exhaustion, which may contribute to the immune suppressed state that occurs in protracted disease. Therapy that reverses T cell exhaustion may restore immune function in immunocompromised patients and improve survival in sepsis.
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