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Neonates harbour highly active γδ T cells with selective impairments in preterm infants
Authors:Deena L. Gibbons  Syeda F. Y. Haque  Tobias Silberzahn  Katherine Hamilton  Cordelia Langford  Peter Ellis  Robert Carr  Adrian C. Hayday
Affiliation:1. Peter Gorer Department of Immunobiology, London, UK;2. National Institute for Health Research (NIHR) Biomedical Research Centre, Guys's and St Thomas' NHS Foundation Trust and King's College London, UK;3. Department of Haematology, King's College London at Guy's Hospital, London, UK;4. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
Abstract:
Acknowledgement of the breadth of T‐cell pleiotropy has provoked increasing interest in the degree to which functional responsiveness is elicited by environmental cues versus differentiation. This is particularly relevant for young animals requiring rapid responses to acute environmental exposure. In young mice, γδ T cells are disproportionately important for immuno‐protection. To examine the situation in humans, we compared populations and clones of T cells from term and preterm babies, and adults. By comparison with αβ T cells, neonate‐derived γδ cells show stronger, pleiotropic functional responsiveness, and lack signatory deficits in IFN‐γ production. Emphasising the acquisition of functional competence in utero, IFN‐γ was produced by γδ cells sampled from premature births, and, although one month's post‐partum environmental exposure invariably increased their TNF‐α production, it had no consistent effect on IFN‐γ or IL‐2. In sum, γδ cells seem well positioned at birth to contribute to immuno‐protection and immuno‐regulation, possibly compensating for selective immaturity in the αβ compartment. With regard to the susceptibilities of preterm babies to viral infection, γδ cells from preterm neonates were commonly impaired in Toll‐like receptor‐3 and ‐7 expression and compared with cells from term babies failed to optimise cytokine production in response to coincident TCR and TLR agonists.
Keywords:Neonate immunity  gd T cells  Toll‐like receptors
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