Presented at the Neonatal Society 2012 Autumn Meeting.
Gibbons DL, Fleming PF, Michel ML, Carr R, Costeloe KL, Hayday AC
Department of Immunobiology, Kings College London, Guys Hospital, London, SE1 9RT, UK
Blizard Institute, Barts and the London School of Medicine and Dentistry, London E1 2AT, UK
Homerton University Hospital NHS Foundation Trust, Homerton Row, London, E9 6SR, UK
Background: T cells are divided on the basis of their T cell receptor (TCR) expression. In peripheral blood the main type of T cells are those that express the αβ TCR. These cells are further divided depending on their expression of key cytokines: Th1 cells making IFNγ; Th2 cells making IL4 and IL13; and Th17 cells making IL17. In preterm and term neonates, Th1 cell functionality appears to be suboptimal which may predispose to infection. In this study we assessed key cytokine production from preterm T-cells. (Approved by the South London REC 2 Committee ID 10/H0802/40)
Methods: Weekly blood samples were taken from preterm babies (23 to 30 weeks gestation) on day 14, 21, 28 and 35 of life. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated with phorbol 12- myristate 13-acetate (PMA) and ionomycin in the presence of brefeldin A for 4 hrs. Cells were stained for surface markers and then analysed for intracellular cytokine production by flow cytometry. Adult PBMCs were used as controls.
Results: As expected, we observed the signatory defect in IFNγ production by Th1 cells in our preterm samples (n=20). However, we also consistently observed significantly more interleukin-8 (IL8) producing CD4 T cells in preterm samples compared to adults (p<0.006). These IL8 producing cells were distinct from T cells making Th1 cytokines (such as IFNγ) or Th2 cytokines (such as IL4 and IL13) or Th17 cytokines (such as IL-17) suggesting a novel T cell population.
Conclusion: Our data propose an unrecognized subset of CD4 T cells in the neonate programmed for IL8 production and apparently distinct from conventional Th1/Th2/Th17 CD4 T cells. Like in adults, it was previously thought that IL8 production in the neonate originated mainly from polymorphonuclear leukocytes and monocytes where it plays an important role in activation of the innate immune response. Our data, however, suggest that the neonatal immune system is enriched with a distinct population of T cells capable of producing large quantities of IL8. Whilst the exact function of these IL8 producing T cells is unclear, their function may be to activate the innate immune response and protect the neonate while the adaptive immune response matures.
Corresponding author: deena.gibbons@kcl.ac.uk