Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high-risk infants.
BACKGROUND
Regulatory T cells (Treg) play an essential role in early immune programming and shaping the immune response towards a pro-allergic or tolerant state. We evaluated cord blood Treg and cytokine responses to microbial and non-microbial stimuli in infants at high risk of allergic disease and their associations with development of allergic disease in the first year.


METHODS
Cord blood mononuclear cells from 72 neonates were cultured with toll-like receptors (TLR2) ligands: lipoteichoic acid (LTA) and heat-killed Lactobacillus rhamnosus GG (HKL); TLR4 ligand: lipopolysaccharide (LPS); ovalbumin (OVA); anti-CD3; or media for 48 h. Treg numbers and Treg cytokines were assessed in relation to allergic disease outcomes during the first year of life (eczema and atopic sensitization).


RESULTS
Infants with eczema (n = 24) had reduced percentages of FoxP3(hi)CD25(hi) Treg in LTA (p = 0.01, adj p = 0.005) and HKL (p = 0.04, adj p = 0.02) stimulated cultures as well as reduced IL-10 (p = 0.01) production following HKL stimulation compared to those without eczema (n = 48). No differences in Treg or cytokine responses to LPS, OVA or anti-CD3 were seen. Infants who developed sensitization had lower percentages of Treg following TLR2 stimulation (but not other stimuli) compared to non-sensitized infants.


CONCLUSIONS
High-risk children who develop allergic disease in the first year of life have deficient Treg responses to microbial stimuli but not allergen from the time of birth, which may contribute to failure of immune tolerance development in infancy.
Allergy and Immune Disorders, Murdoch Children's Research Institute, Melbourne, Vic., Australia; Department of Paediatrics, University of Melbourne, Melbourne, Vic., Australia; Department of Paediatrics, Universiti Putra Malaysia, Selangor, Malaysia.
Intan H
IH
Ismail
Robert J
RJ
Boyle
Li-Jeen
LJ
Mah
Paul V
PV
Licciardi
Mimi L K
ML
Tang
D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004485:Eczema / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D007231:Infant, Newborn; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D012306:Risk; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013682:Teichoic Acids / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4
D000942:Antigens, Bacterial; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C009900:lipoteichoic acid
atopic sensitization; cord blood; cytokines; eczema; infants; microbial stimuli; neonates; regulatory T cell; toll-like receptor