Altered immune cell profiles and impaired CD4 T-cell activation in single and multi-food allergic adolescents.

Abstract

Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare. In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence. We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls. We show that food allergic adolescents have higher circulating proportions of dendritic cells (p=.0084, FDR-adjusted p=.087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p=.011, FDR-adjusted p=.087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naïve CD4 T cells from food allergic adolescents produced less IL-6 (p=.0020, FDR-adjusted p=.018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p=.0044, FDR-adjusted p=.020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p=.035, FDR-adjusted p=.11, median in no FA: 6.29, in FA: 5.67) than naïve CD4T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines. These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.