Impairment of T-regulatory cells in cord blood of atopic mothers

J Allergy Clin Immunol. 2008 Jun;121(6):1491-9, 1499.e1-13. doi: 10.1016/j.jaci.2008.04.010.

Abstract

Background: Maternal atopy is a strong predictor for the development of childhood allergic diseases. The underlying mechanisms are ill defined, yet regulatory T (Treg) and T(H)17 cells may play a key role potentially shaping the early immune system toward a proallergic or antiallergic immune regulation.

Objective: We examined T(H)1/T(H)2, Treg, and T(H)17 cell responses to innate (lipid A/peptidoglycan) and mitogen/adaptive (phytohemagglutinin/Dermatophagoides pteronyssinus 1) immune stimulation in cord blood from offspring of atopic/nonatopic mothers.

Methods: Cord blood mononuclear cells from 161 healthy neonates (59% nonatopic, 41% atopic mothers) were investigated regarding Treg and T(H)17 cells (mRNA/surface markers), suppressive function, and proliferation/cytokine secretion.

Results: Cord blood from offspring of atopic mothers showed fewer innate-induced Treg cells (CD4(+)CD25(+)high), lower mRNA expression of associated markers (glucocorticoid-induced tumor necrosis factor receptor-related protein/lymphocyte activation gene 3; P < .05), and a trend toward lower Forkhead box transcription factor 3 (Foxp3) expression. Treg cell function was impaired in mitogen-induced suppression of T effector cells in cord blood of offspring from atopic mothers (P = .03). Furthermore, IL-10 and IFN-gamma secretion were decreased in innate-stimulated cord blood of offspring from atopic mothers (P = .04/.05). Innate-induced IL-17 was independent of maternal atopy and highly correlated with IL-13 secretion.

Conclusion: In offspring of atopic mothers, Treg cell numbers, expression, and function were impaired at birth. T(H)17 cells were correlated with T(H)2 cells, independently of maternal atopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / biosynthesis
  • CTLA-4 Antigen
  • Cytokines / biosynthesis
  • Female
  • Fetal Blood / cytology
  • Fetal Blood / immunology*
  • Flow Cytometry
  • Forkhead Transcription Factors / biosynthesis
  • Gene Expression
  • Glucocorticoid-Induced TNFR-Related Protein
  • Humans
  • Hypersensitivity, Immediate / immunology*
  • Infant, Newborn / immunology*
  • Male
  • Mothers
  • RNA, Messenger / analysis
  • Receptors, Nerve Growth Factor / biosynthesis
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / biosynthesis

Substances

  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoid-Induced TNFR-Related Protein
  • RNA, Messenger
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF18 protein, human
  • Transforming Growth Factor beta