title: T-cell activation genes differentially expressed at birth in CD4+ T-cells from children who develop IgE food allergy.
abstract: BACKGROUND
  Presymptomatic immaturity in neonatal T-cell function is a consistent antecedent of allergic disease, including reduced responsiveness to polyclonal activation.
  
  
  METHODS
  To elucidate the underlying mechanisms, we examined for differences in T-cell gene expression in longitudinal samples collected at birth and at 1 year of age in children with (n = 30) and without IgE-mediated food allergy (n = 30). We employed a low-level soluble anti-CD3 stimulus to activate the T-cell receptor (TCR) and surveyed gene expression by DNA microarray in purified CD4(+) T-cells. Allergen-specific responses were assessed in parallel functional studies.
  
  
  RESULTS
  At birth, the allergic group showed a reduced number of genes up regulated in response to anti-CD3 treatment on the microarray and a reduced lympho proliferative capacity, suggesting clear differences in T-cell signalling pathways. Polymerase chain reaction (PCR) validation of candidate genes confirmed significantly lower expression of a number of genes in the allergic group including RELB, NFKB2, LIF and FAS. By 12 months of age, there were marked changes in the anti-CD3 response in all infants, culminating in upregulation of cytokine genes (IL-5, IL-13, IL-17 and IL-22). Neonatal differences were no longer apparent. Instead, the allergic group, all symptomatic by this age, showed differential expression of T-cell lineage pathways including GATA-3, MAL and FcER1 in unstimulated T-cells. Allergen stimulation induced significantly higher cytokines production (IL-5, IL-13 and IFNγ) in the allergic group.
  
  
  CONCLUSIONS
  Although transient, suboptimal neonatal T-cell activation pathways that signal through the NF-κB complex may affect the developmental transition of T-cell phenotypes in the periphery shortly after birth and may increase the risk of food allergy.
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Martino
authors.forename: A
authors.initials: A
authors.lastname: Bosco
authors.forename: K L
authors.initials: KL
authors.lastname: McKenna
authors.forename: E
authors.initials: E
authors.lastname: Hollams
authors.forename: D
authors.initials: D
authors.lastname: Mok
authors.forename: P G
authors.initials: PG
authors.lastname: Holt
authors.forename: S L
authors.initials: SL
authors.lastname: Prescott
mesh_terms: D000485:Allergens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016000:Cluster Analysis; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005512:Food Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000485:Allergens; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell