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Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants



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 commensals1,2,3. 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.

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Figure 1: CXCL8-producing T cells in infants.
Figure 2: The surface phenotype of CXCL8-producing T cells.
Figure 3: Flagellin co-stimulates CXCL8 production from neonatal T cells.
Figure 4: Infants with illness display CXCL8-producing T cells.

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  1. Zaghouani, H., Hoeman, C.M. & Adkins, B. Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells. Trends Immunol. 30, 585–591 (2009).

    CAS  Article  Google Scholar 

  2. Hebel, K. CD4+ T cells from human neonates and infants are poised spontaneously to run a non-classical IL-4 program. J. Immunol. 192, 5160–5170 (2014).

    CAS  Article  Google Scholar 

  3. Gibbons, D.L. et al. Neonates harbour highly active γδ T cells with selective impairments in preterm infants. Eur. J. Immunol. 39, 1794–1806 (2009).

    CAS  Article  Google Scholar 

  4. Carr, R., Brocklehurst, P., Dore, C.J. & Modi, N. Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial. Lancet 373, 226–233 (2009).

    CAS  Article  Google Scholar 

  5. Berrington, J.E., Hearn, R.I., Bythell, M., Wright, C. & Embleton, N.D. Deaths in preterm infants: changing pathology over 2 decades. J. Pediatr. 160, 49–53.e1 (2012).

    Article  Google Scholar 

  6. Costeloe, K.L. et al. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). Br. Med. J. 345, e7976 (2012).

    Article  Google Scholar 

  7. Junge, S. et al. Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. Eur. J. Immunol. 37, 3270–3280 (2007).

    CAS  Article  Google Scholar 

  8. Kimmig, S. et al. Two subsets of naïve T-helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med. 195, 789–794 (2002).

    CAS  Article  Google Scholar 

  9. Mold, J.E. et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 322, 1562–1565 (2008).

    CAS  Article  Google Scholar 

  10. Sharma, N., Akhade, A.S. & Qadri, A. Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells. J. Leukoc. Biol. 93, 521–528 (2013).

    CAS  Article  Google Scholar 

  11. Luster, A.D. Chemokines—chemotactic cytokines that mediate inflammation. N. Engl. J. Med. 338, 436–445 (1998).

    CAS  Article  Google Scholar 

  12. Zlotnik, A. & Yoshie, O. The chemokine superfamily revisited. Immunity 36, 705–716 (2012).

    CAS  Article  Google Scholar 

  13. De Rosa, S.C. et al. Ontogeny of γδ T cells in humans. J. Immunol. 172, 1637–1645 (2004).

    CAS  Article  Google Scholar 

  14. Khalaf, H., Jass, J. & Olsson, P.E. The role of calcium, NF-κB and NFAT in the regulation of CXCL8 and IL-6 expression in Jurkat T-cells. Int. J. Biochem. Mol. Biol. 4, 150–156 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Nanthakumar, N.N., Fusunyan, R.D., Sanderson, I. & Walker, W.A. Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis. Proc. Natl. Acad. Sci. USA 97, 6043–6048 (2000).

    CAS  Article  Google Scholar 

  16. Levy, E. et al. Distinct roles of TLR4 and CD14 in LPS-induced inflammatory responses of neonates. Pediatr. Res. 66, 179–184 (2009).

    CAS  Article  Google Scholar 

  17. Thornton, N.L., Cody, M.J. & Yost, C.C. Toll-like receptor 1/2 stimulation induces elevated interleukin-8 secretion in polymorphonuclear leukocytes isolated from preterm and term newborn infants. Neonatology 101, 140–146 (2012).

    CAS  Article  Google Scholar 

  18. Taur, Y. et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoetic stem cell transplantation. Clin. Infect. Dis. 55, 905–914 (2012).

    CAS  Article  Google Scholar 

  19. Chiaretti, S. et al. Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival. Blood 103, 2771–2778 (2004).

    CAS  Article  Google Scholar 

  20. Heeger, P.S. et al. Decay-accelerating factor modulates induction of T cell immunity. J. Exp. Med. 201, 1523–1530 (2005).

    CAS  Article  Google Scholar 

  21. Pelletier, M. et al. Evidence for a cross-talk between human neutrophils and Th17 cells. Blood 115, 335–343 (2010).

    CAS  Article  Google Scholar 

  22. Taylor, P.R. et al. Activation of neutrophils by autocrine IL17A–IL17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγT and dectin-2. Nat. Immunol. 15, 143–151 (2014).

    CAS  Article  Google Scholar 

  23. Schröder, J.M., Mrowietz, U. & Christophers, E. Purification and partial biologic characterization of a human lymphocyte-derived peptide with potent neutrophil-stimulating activity. J. Immunol. 140, 3534–3540 (1988).

    PubMed  Google Scholar 

  24. Kyriakakis, E. et al. Invariant natural killer T cells: linking inflammation and neovascularization in human atherosclerosis. Eur. J. Immunol. 40, 3268–3279 (2010).

    CAS  Article  Google Scholar 

  25. Dagna, L. et al. Skewing of cytotoxic activity and chemokine production, but not of chemokine receptor expression, in human type-1/-2 γδ T lymphocytes. Eur. J. Immunol. 32, 2934–2943 (2002).

    CAS  Article  Google Scholar 

  26. Laggner, U. et al. Identification of a novel proinflammatory human skin-homing Vg9Vd2 T cell subset with a potential role in psoriasis. J. Immunol. 187, 2783–2793 (2011).

    CAS  Article  Google Scholar 

  27. Himmel, M.E. et al. Human CD4+ FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils. Eur. J. Immunol. 41, 306–312 (2011).

    CAS  Article  Google Scholar 

  28. Schaerli, P. et al. Characterization of human T cells that regulate neutrophilic skin inflammation. J. Immunol. 173, 2151–2158 (2004).

    CAS  Article  Google Scholar 

  29. Chorro, L. & Geissmann, F. Development and homeostasis of 'resident' myeloid cells: the case of the Langerhans cell. Trends Immunol. 31, 438–445 (2010).

    CAS  Article  Google Scholar 

  30. Havran, W.L. & Allison, J.P. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature 335, 443–445 (1988).

    CAS  Article  Google Scholar 

  31. Mold, J.E. et al. Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans. Science 330, 1695–1699 (2010).

    CAS  Article  Google Scholar 

  32. Carr, R. The role of colony stimulating factors and immunoglobulin in the prevention and treatment of neonatal infection. Arch. Dis. Child. Fetal Neonatal Ed. 98, F192–F194 (2013).

    Article  Google Scholar 

  33. Panero, A. et al. Interleukin 6 in neonates with early and late onset infection. Pediatr. Infect. Dis. J. 16, 370–375 (1997).

    CAS  Article  Google Scholar 

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We thank P. Hunter for helpful discussions, T. Hayday for flow cytometry, K. Rouault-Pierre (London Research Institute, Cancer Research UK) for cord blood, Pierre Vantourout (London Research Institute, Cancer Research UK) for γδ T cell lines, M. Greaves for advice on T-ALL, P. Chakravarty for microarray analysis and M. Leite-de-Moraes for support of mouse studies. P.F. was funded by a strategic research grant from the Barts and the London Charity, A.V. and N.J.S. by the UK National Institute for Health Research (NIHR) Great Ormond Street Hospital (GOSH) Biomedical Research Centre (BRC), N.J.S. partly by GOSH Children's charity, and D.G., R.C. and A.H. by the Guy's and St. Thomas', charity, the NIHR Biomedical Research Centre at Guy's and St. Thomas', Hospital and King's College, and by a Wellcome Trust Programme Grant to A.H.

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Authors and Affiliations



D.G. co-designed the study, undertook all experiments with human materials, evaluated the results and co-wrote the manuscript; P.F. co-designed the study, was attending physician to the clinical trial to which the study is annexed, provided human samples, evaluated clinical data and edited the manuscript; A.V. undertook the immunohistology; M.-L.M. undertook the animal model experiments; N.J.S. evaluated immunohistology and provided samples; K.C. designed and supervised the clinical trial to which the study is annexed and edited the manuscript; R.C. co-formulated the study as an annex to a clinical trial and edited the manuscript; N.K. co-supervised the analysis of pathology and edited the manuscript; A.H. co-designed the study, evaluated the results and co-wrote the manuscript.

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Correspondence to Deena Gibbons or Adrian Hayday.

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The authors declare no competing financial interests.

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Gibbons, D., Fleming, P., Virasami, A. et al. Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants. Nat Med 20, 1206–1210 (2014).

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