title: γδ T cells protect against LPS-induced lung injury.
abstract: γδ T lymphocytes are a unique T cell population with important anti-inflammatory capabilities. Their role in acute lung injury, however, is poorly understood but may provide significant insight into lung-protective mechanisms occurring after injury. In a murine model of lung injury, wild-type C57BL/6 and TCRδ(-/-) mice were exposed to Escherichia coli LPS, followed by analysis of γδ T cell and macrophage subsets. In the absence of γδ T cells, TCRδ(-/-) mice developed increased inflammation and alveolar-capillary leak compared with wild-type C57BL/6 mice after LPS exposure that correlated with expansion of distinct macrophage populations. Classically activated M1 macrophages were increased in the lung of TCRδ(-/-) mice at d 1, 4, and 7 after LPS exposure that peaked at d 4 and persisted at d 7 compared with wild-type animals. In response to LPS, Vγ1 and Vγ7 γδ T cells were expanded in the lung and expressed IL-4. Coculture experiments showed decreased expression of TNF-α by resident alveolar macrophages in the presence of γδ T cells that was reversed in the presence of an anti-IL-4-blocking antibody. Treatment of mice with rIL4 resulted in reduced numbers of M1 macrophages, inflammation, and alveolar-capillary leak. Therefore, one mechanism by which Vγ1 and Vγ7 γδ T cells protect against LPS-induced lung injury is through IL-4 expression, which decreases TNF-α production by resident alveolar macrophages, thus reducing accumulation of M1 macrophages, inflammation, and alveolar-capillary leak.
authors.affiliation: Departments of *Medicine and Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Wehrmann
authors.affiliation: Departments of *Medicine and Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Lavelle
authors.affiliation: Departments of *Medicine and Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Colm B
authors.initials: CB
authors.lastname: Collins
authors.affiliation: Departments of *Medicine and Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Alex N
authors.initials: AN
authors.lastname: Tinega
authors.affiliation: Departments of *Medicine and Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Thurman
authors.affiliation: Departments of *Medicine and Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Burnham
authors.affiliation: Departments of *Medicine and Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA philip.simonian@ucdenver.edu.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Simonian
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019559:Capillary Leak Syndrome / Q000209:etiology; D018920:Coculture Techniques; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D007249:Inflammation; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000145:classification / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C482199:lipopolysaccharide, E coli O55-B5; D015847:Interleukin-4
keywords: ARDS; IL-4; TNF-α; alveolar-capillary leak; macrophages