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T-cell activation genes differentially expressed at birth in CD4(+) T-cells from children who develop IgE food allergy.

Authors: Martino, DJ  Bosco, A  McKenna, KL  Hollams, E  Mok, D  Holt, PG  Prescott, SL 
Citation: Martino DJ, etal., Allergy. 2012 Feb;67(2):191-200. doi: 10.1111/j.1398-9995.2011.02737.x. Epub 2011 Nov 11.
Pubmed: (View Article at PubMed) PMID:22077487

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. 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 IFNgamma) in the allergic group. Conclusion: Although transient, suboptimal neonatal T-cell activation pathways that signal through the NF-kappaB complex may affect the developmental transition of T-cell phenotypes in the periphery shortly after birth and may increase the risk of food allergy.


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CRRD Object Information
CRRD ID: 5687145
Created: 2012-02-01
Species: All species
Last Modified: 2012-02-01
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.