Preterm cord blood CD4⁺ T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4⁺ T cells in bronchopulmonary dysplasia

Hum Immunol. 2015 May;76(5):329-338. doi: 10.1016/j.humimm.2015.03.007. Epub 2015 Mar 20.


Background: Chorioamnionitis (CA) is associated with premature delivery and bronchopulmonary dysplasia (BPD). We hypothesize that preterm infants exposed to CA have reduced suppressive regulatory T cells (Treg) and increased non-regulatory T cell pro-inflammatory cytokines, increasing risk for BPD.

Objective: To evaluate cord blood CD4(+) T cell regulatory phenotype and pro-inflammatory cytokine production in CA and BPD groups.

Study design: Cord blood mononuclear cells from infants (GA ⩽32 weeks), with or without placental histological evidence of CA (hChorio), were analyzed by flow cytometry. Clinical information was collected by retrospective chart review. Numbers of putative Treg (CD4(+)FoxP3(+)CD25(+)CD127Dim), CD4(+) non-Tregs, and CD4(+) T cell intracellular cytokine content following in vitro stimulation were compared with CA status and oxygen requirement at 36weeks postmenstrual age.

Result: Absolute Treg numbers were not different in CA and non-CA exposed samples. However, the infants who developed BPD had a significant decrease in Treg and non-regulatory T cell numbers. Greater IL-6 production was observed in hCA group.

Conclusion: A pro-inflammatory CD4(+) T cell status is noted in CA and BPD but the later disease is also associated with decrease in Tregs, suggesting that the development of BPD is marked by distinct inflammatory changes from those of CA exposed infants.

Keywords: Bronchopulmonary dysplasia; CD4(+) T cells; Chorioamnionitis; Cord blood mononuclear cell; IL-6.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchopulmonary Dysplasia / immunology*
  • CD4 Antigens / metabolism
  • Cells, Cultured
  • Chorioamnionitis / immunology*
  • Female
  • Fetal Blood / immunology*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Infant, Newborn
  • Inflammation Mediators / metabolism*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Pregnancy
  • Premature Birth / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Inflammation Mediators
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-6