Neonatal T-cell maturation and homing receptor responses to Toll-like receptor ligands differ from those of adult naive T cells: relationship to prematurity

Pediatr Res. 2012 Feb;71(2):136-43. doi: 10.1038/pr.2011.26. Epub 2011 Dec 21.

Abstract

Introduction: Inflammation and infection are associated with premature birth and with activation of the fetal immune system. We hypothesized that exposure to microbial Toll-like receptor (TLR) ligands plays an important role in neonatal T-cell maturation and that early exposure to microbial products may result in early T-cell maturation and a tendency for these matured effector cells to change their homing receptor patterns.

Results: Expression of the CD45RO marker was induced in term neonatal T cells after in vitro exposure to TLR ligands for 7 days. Interestingly, naive T cells from adult blood were unaffected by TLR ligand exposure. In addition, neonatal T cells had more cells with decreased expression of the α4β7 integrins and increased expression of CCR4 after in vitro exposure of TLR ligands-similar to the expression of these molecules in adult naive T cells.

Discussion: These findings are relevant for the understanding of neonatal T-cell maturation and may contribute to our understanding of multiorgan inflammatory complications of prematurity.

Methods: Cord blood was obtained from term and preterm infants. Using flow cytometry, we identified a mature (CD45RO(+)) phenotype in preterm infant cord blood (CB) T cells that had decreased expression of the α4β7 integrins and increased expression of the C-C chemokine receptor 4 (CCR4) as compared with term infant CB.

Publication types

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

MeSH terms

  • Adult
  • Age Factors
  • Aging / immunology*
  • Case-Control Studies
  • Cells, Cultured
  • Chorioamnionitis / immunology
  • Chorioamnionitis / microbiology
  • Female
  • Fetal Blood / immunology
  • Flow Cytometry
  • Gestational Age
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Memory
  • Immunophenotyping
  • Infant, Newborn
  • Infant, Premature / blood
  • Infant, Premature / immunology*
  • Integrins / metabolism
  • Leukocyte Common Antigens / metabolism
  • Ligands
  • Lymphocyte Activation
  • Phenotype
  • Pregnancy
  • Premature Birth / blood
  • Premature Birth / immunology*
  • Premature Birth / microbiology
  • Receptors, CCR4 / metabolism
  • Receptors, Lymphocyte Homing / drug effects
  • Receptors, Lymphocyte Homing / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / metabolism*
  • United States

Substances

  • CCR4 protein, human
  • Immunologic Factors
  • Integrins
  • Ligands
  • Receptors, CCR4
  • Receptors, Lymphocyte Homing
  • Toll-Like Receptors
  • integrin alpha4beta7
  • Leukocyte Common Antigens