Characterising the maturation of T cell polarisation in preterm and term infants and in neonatal chronic lung disease — ASN Events
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  2. Workshop 6: Inflammatory Diseases and Mechanisms
  3. Characterising the maturation of T cell polarisation in preterm and term infants and in neonatal chronic lung disease

Characterising the maturation of T cell polarisation in preterm and term infants and in neonatal chronic lung disease (#63)

Jason Lao 1 , Merrin Pang 1 , Steven X Cho 1 , Niamh E Mangan 2 , Alex Veldman 1 , Camden Y Lo 1 , Friederike Beker 3 , Clare Collins 4 , Omar Kamlin 5 , Kai Konig 4 , Atul Malhotra 6 7 , Kenneth Tan 7 , Christiane Theda 5 , Philip J Berger 1 , Claudia A Nold 1 , Marcel F Nold 1
  1. Monash University, Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. Hudson Institute of Medical Research, Clayton, VIC, Australia
  3. Mater Hospital, Brisbane, QLD, Australia
  4. Mercy Hospital, Melbourne, VIC, Australia
  5. Royal Women's Hospital, Melbourne, VIC, Australia
  6. Department of Paediatrics, Monash University, Melbourne, VIC, Australia
  7. Monash Newborn, Monash Health, Melbourne, VIC, Australia

Background: Bronchopulmonary dysplasia (BPD) is a common neonatal lung disease that is underpinned by pulmonary inflammation. Despite extensive research, a dominant immune pathway that drives BPD remains elusive, and hardly any information exists on adaptive immunity in BPD and on the immune system’s longitudinal development in preterm and term infants.

Methods: Cord and peripheral blood was collected from: i) infants born at 24-29 gestational weeks at birth, on days 1, 7 and 14, and at 36 weeks corrected gestational age (cGA); ii) healthy term infants at birth and at a postnatal timepoint (4-16 weeks); iii) healthy adults. Cells were stimulated with either PMA+ionomycin or vehicle overnight, followed by enumeration of the Th1 (signature cytokine IFNγ), Th2 (IL-4), Th17 (IL-17A) and regulatory T cell (Treg) subsets by flow cytometry. Results were analysed against BPD disease status, taking clinical events such as respiratory support, sepsis and medication into account.

Results: 51 preterm infants, 20 term infants and 5 adults were enrolled, and 258 unique samples collected. Th2 polarisation predominated in preterm and term infants up to 16 weeks of age, with up to 62% of all CD4+ T cells being IL-4+ vs 2% in adults. Baseline IFNγ- and IL-17A-positivity was low in all groups; inducibility of both Th1 and Th17 polarisation developed at the age of 16 weeks. The percentage of Treg was 5-fold higher in infants than in adults. The 36 preterm infants who suffered from BPD exhibited up to 36-fold increased frequencies of IL-4+CD4+ Th2 cells at most timepoints.

Conclusions: Our study explores the virtually uncharted territory of maturation of the immune system in preterm and term infants. An important finding is that the severe chronic lung disease BPD is associated with strong Th2 polarisation, suggesting that therapies targeting the Th2 pathway may offer benefit to the tiny BPD patients.

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