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T‐cell activation genes differentially expressed at birth in CD4 + T‐cells from children who develop IgE food allergy
Author(s) -
Martino D. J.,
Bosco A.,
McKenna K. L.,
Hollams E.,
Mok D.,
Holt P. G.,
Prescott S. L.
Publication year - 2012
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2011.02737.x
Subject(s) - immunology , immunoglobulin e , allergy , cd3 , t cell , t cell receptor , biology , microbiology and biotechnology , immune system , antibody , cd8
To cite this article: Martino DJ, Bosco A, McKenna KL, Hollams E, Mok D, Holt PG, Prescott SL. T‐cell activation genes differentially expressed at birth in CD4 + T‐cells from children who develop IgE food allergy. Allergy 2012; 67 : 191–200.AbstractBackground: 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.Conclusion: 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.