title: Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants.
abstract: In spite of their precipitous encounter with the environment, newborn infants cannot readily mount T helper type 1 (TH1) cell antibacterial and antiviral responses. Instead, they show skewing toward TH2 responses, which, together with immunoregulatory functions, are thought to limit the potential for inflammatory damage, while simultaneously permitting intestinal colonization by commensals. However, these collective capabilities account for relatively few T cells. Here we demonstrate that a major T cell effector function in human newborns is interleukin-8 (CXCL8) production, which has the potential to activate antimicrobial neutrophils and γδ T cells. CXCL8 production was provoked by antigen receptor engagement of T cells that are distinct from those few cells producing TH1, TH2 and TH17 cytokines, was co-stimulated by Toll-like receptor signaling, and was readily apparent in preterm babies, particularly those experiencing neonatal infections and severe pathology. By contrast, CXCL8-producing T cells were rare in adults, and no equivalent function was evident in neonatal mice. CXCL8 production counters the widely held view that T lymphocytes in very early life are intrinsically anti-inflammatory, with implications for immune monitoring, immune interventions (including vaccination) and immunopathologies. It also emphasizes qualitative distinctions between infants' and adults' immune systems.
authors.affiliation: 1] Peter Gorer Department of Immunobiology, King's College London, London, UK. [2] London Research Institute, Cancer Research UK, London, UK.
authors.forename: Deena
authors.initials: D
authors.lastname: Gibbons
authors.affiliation: 1] Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. [2] Department of Neonatology, Homerton University Hospital, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Fleming
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Virasami
authors.affiliation: 1] Peter Gorer Department of Immunobiology, King's College London, London, UK. [2] London Research Institute, Cancer Research UK, London, UK.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Michel
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.affiliation: 1] Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. [2] Department of Neonatology, Homerton University Hospital, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Costeloe
authors.affiliation: Department of Haematology, King's College London, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Carr
authors.affiliation: 1] Great Ormond Street Hospital, London, UK. [2] Institute of Child Health, University College London, London, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
authors.affiliation: 1] Peter Gorer Department of Immunobiology, King's College London, London, UK. [2] London Research Institute, Cancer Research UK, London, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Hayday
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn / Q000097:blood / Q000276:immunology*; D007234:Infant, Premature / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; D016209:Interleukin-8