title: Neonatal regulatory T cells have reduced capacity to suppress dendritic cell function.
abstract: Regulatory T cells (Treg cells) limit contact between dendritic cells (DCs) and conventional T cells (Tcons), decreasing the formation of aggregates as well as down-modulating the expression of co-stimulatory molecules by DCs, thus decreasing DC immunogenicity and abrogating T-cell activation. Despite the importance of this Treg-cell function, the capacity of Treg cells from term and preterm neonates to suppress DCs, and the suppressive mechanisms they use, are still undefined. We found that, relative to adult Treg cells, activated Treg cells from human neonates expressed lower FOXP3 and CTLA-4, but contained higher levels of cAMP. We developed an in vitro model in which Treg function was measured at a physiological ratio of 1 Treg for 10 Tcon and 1 monocyte-derived DC, as Treg target. Term and preterm Treg cells failed to suppress the formation of DC-Tcon aggregates, in contrast to naïve and memory Treg cells from adults. However, neonatal Treg cells diminished DC and Tcon activation as well as actin polymerization at the immunological synapses. In addition, CTLA-4 and cAMP were the main suppressive molecules used by neonatal Treg. Altogether, both preterm and term neonatal Treg cells appear less functional than adult Treg cells, and this defect is consistent with the general impairment of CD4 cell function in newborns.
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Rueda
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Moreno-Fernandez
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Jackson
authors.affiliation: Division of Neonatology/Pulmonary Biology, the Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH, USA.
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.affiliation: Division of Neonatology/Pulmonary Biology, the Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH, USA.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Chougnet
mesh_terms: D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000328:Adult; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002469:Cell Separation; D000242:Cyclic AMP / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D054992:Immunological Synapses / Q000737:chemistry / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D000199:Actins; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D000242:Cyclic AMP
keywords: Cellular immunology; Dendritic cells; Neonate immunity; Regulatory T cells; T cells