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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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.
Source Data for Supplementary Figures 1–7
About this article
Nature Reviews Immunology (2017)