Defining T helper cell immunity in bronchopulmonary dysplasia

Abstract

Abstract Background Bronchopulmonary dysplasia (BPD) is a common neonatal lung disease that has been linked to pulmonary inflammation. Previous studies have suggested involvement of various cell types and soluble factors but have thus far failed to reveal a dominant pathway that underpins disease progression. It remains unknown that which T helper (Th) cell polarization, if any, contributes to the pathogenesis of BPD. Methods Citrated whole cord and peripheral blood were collected from infants born between 24+0–28+6 gestational weeks at five different time points, namely at birth, on days 1, 7 and 14 and at 36 weeks corrected gestational age (CGA). Cells were stimulated with either PMA, ionomycin and brefeldin A or vehicle and brefeldin A overnight. Cells were then stained for multi-color flow cytometry to enumerate Th cell subsets including Th1, Th2 and Th17 and regulatory T cells. Results were analyzed against BPD disease status at 36 weeks CGA and corrected for confounders. Results 50 infants were enrolled and 228 unique samples were collected. 36 enrolled infants (72%) had BPD (mild to severe) at 36 weeks CGA. When compared to infants that did not have the disease, the frequency of interleukin(IL)-4 in CD4+ Th cells in peripheral blood was increased in infants with BPD on days 1 (p=0.0449), 7 (p=0.0423), 14 (p=0.0489) and 36 weeks CGA but not within cord blood. There was no difference in the frequency of cells positive for interferon-gamma (IFNγ), IL-17A or FOXP3 among CD4+ cells in blood from BPD and non-BPD infants across all time points. Conclusions T helper cells are polarized towards a Th2 phenotype in infants with BPD based on elevated levels of IL-4 in CD4+ cells. We hypothesize that BPD infants may benefit from therapies that target the Th2 pathway.