title: Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia.
abstract: Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng/kg) was administered intravenously in 15 healthy volunteers. Peripheral blood and bronchoalveolar lavage fluid (BALF) were collected at baseline and after 2, 4, 6, 8, and 24 hours for flow cytometry. CD4+CD25+CD127lowFoxp3+regulatory T cells (Tregs), CD4+CD161+cells, and activated Human leukocyte antigen, HLA-DR+CD38+T cells were determined. Ex vivo whole-blood cytokine production and Toll-like receptor (TLR)-4 expression on Tregs were measured. Absolute number of CD3+CD4+(P = .026), CD3+CD8+(P = .046), Tregs (P = .023), and CD4+CD161+cells (P = .042) decreased after endotoxin administration. The frequency of anti-inflammatory Tregs increased (P = .033), whereas the frequency of proinflammatory CD4+CD161+cells decreased (P = .034). Endotoxemia was associated with impaired whole-blood production of tumor necrosis factor-α, interleukin-10, IL-6, IL-17, IL-2, and interferon-γ in response to phytohaemagglutinin but did not affect TLR4 expression on Tregs. No changes in the absolute count or frequency of BALF T cells were observed. Systemic inflammation is associated with lymphopenia, a relative increase in the frequency of anti-inflammatory Tregs, and a functional impairment of T-cell cytokine production.
authors.affiliation: Department of Infectious Diseases 8632, Viro-immunology Research Unit, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.|Department of Clinical Immunology 2034, Blood Bank, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ronit
authors.affiliation: Department of Intensive Care, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.|Department of Anaesthesia, Køge Hospital, Køge, Denmark.
authors.forename: Ronni R
authors.initials: RR
authors.lastname: Plovsing
authors.affiliation: Department of Infectious Diseases 8632, Viro-immunology Research Unit, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.|Department of Clinical Immunology 2034, Blood Bank, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Gaardbo
authors.affiliation: Department of Intensive Care, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.|Department of Infectious Diseases 7641, Centre of Inflammation and Metabolism, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Ronan M G
authors.initials: RM
authors.lastname: Berg
authors.affiliation: Department of Infectious Diseases 8632, Viro-immunology Research Unit, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.|Department of Clinical Immunology 2034, Blood Bank, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hartling
authors.affiliation: Department of Clinical Immunology 2034, Blood Bank, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.affiliation: Department of Infectious Diseases 8632, Viro-immunology Research Unit, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Åse B
authors.initials: ÅB
authors.lastname: Andersen
authors.affiliation: Department of Clinical Immunology, Tissue Typing Laboratory 7631, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.affiliation: Department of Infectious Diseases 7641, Centre of Inflammation and Metabolism, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.|Department of Neuroanaesthesiology, Neurointensive Care Unit 2093, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
authors.affiliation: Department of Infectious Diseases 8632, Viro-immunology Research Unit, University Hospital Rigshospitalet, Copenhagen Ø, Denmark sdn@dadlnet.dk.
authors.forename: Susanne D
authors.initials: SD
authors.lastname: Nielsen
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D019446:Endotoxemia / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D004731:Endotoxins / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D004731:Endotoxins
keywords: CD161; T cells; bronchoalveolar lavage fluid; endotoxin; human experimentation; inflammation; regulatory T cells; sepsis