title: Preterm cord blood CD4⁺ T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4⁺ T cells in bronchopulmonary dysplasia.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pediatrics, Neonatology Division, Golisano Children's Hospital.
authors: Ravi
authors: R
authors: Misra
authors: Department of Pediatrics, Neonatology Division, Golisano Children's Hospital.
authors: Syed
authors: S
authors: Shah
authors: Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology.
authors: Deborah
authors: D
authors: Fowell
authors: Department of Biostatistics and Computational Biology.
authors: Hongyue
authors: H
authors: Wang
authors: Department of Pediatrics, Neonatology Division, Golisano Children's Hospital.
authors: Kristin
authors: K
authors: Scheible
authors: Department of Pediatrics, Neonatology Division, Golisano Children's Hospital.
authors: Sara
authors: S
authors: Misra
authors: Department of Pediatrics, Neonatology Division, Golisano Children's Hospital.
authors: Heidie
authors: H
authors: Huyck
authors: Department of Pediatrics, Neonatology Division, Golisano Children's Hospital.
authors: Claire
authors: C
authors: Wyman
authors: Department of Pediatrics, Medical University of South Carolina, Charleston, SC29425.
authors: Rita M
authors: RM
authors: Ryan
authors: Department of Pediatrics, University at Buffalo, Buffalo, NY, 14222, United States.
authors: Anne Marie
authors: AM
authors: Reynolds
authors: Department of Pediatrics, Neonatology Division, Golisano Children's Hospital.|Pediatric Molecular and Personalized Medicine Program.
authors: Tom
authors: T
authors: Mariani
authors: Department of Pathology and Laboratory Medicine University of Rochester Medical Center (URMC), Rochester, NY 14642..
authors: Philip J
authors: PJ
authors: Katzman
authors: Department of Pediatrics, Neonatology Division, Golisano Children's Hospital.
authors: Gloria S
authors: GS
authors: Pryhuber
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D002821:Chorioamnionitis / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6
keywords: Bronchopulmonary dysplasia; CD4(+) T cells; Chorioamnionitis; Cord blood mononuclear cell; IL-6