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

To show underlying mechanisms, we examined differences in T-cell gene expression in samples at birth and at 1 year in children with and without IgE allergy.

Authors:

Martino, D. J.; Bosco, A.; McKenna, K. L.; Hollams, E.; Mok, D.; Holt, P. G.; Prescott, S. L.

Authors notes:

Allergy. 2012;67(2):191-200

Keywords:

food allergy, gene profiling, IgE food allergy, NF-κB, ovalbumin, pathways analysis, RELB, signal transduction, T-cell receptor

Abstract

Presymptomatic immaturity in neonatal T-cell function is a consistent antecedent of allergic disease, including reduced responsiveness to polyclonal activation.

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.

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.

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.