Elevated expression of activated TH2 cells and milk-specific TH2 cells in milk-induced eosinophilic esophagitis

Abstract

Background: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Esophageal biopsy specimens are characterized by eosinophilia and expression of T_H2 cytokines.

Objective: To ascertain whether T_H2 cells can exist in the peripheral blood in patients with milk-induced EoE.

Methods: Peripheral blood mononuclear cells from 20 children with milk-induced EoE were collected during active EoE (EoE-A) while consuming milk and inactive EoE (EoE-I) while not consuming milk, and 8 healthy patients without EoE were used as controls. The samples were analyzed for T-cell phenotype, including intracellular cytokines before and after incubation with milk antigens and assessed by flow cytometry.

Results: We found a significant increase in CD4⁺ T_H2 cells in the peripheral blood of patients with EoE-A compared with the controls. Furthermore, we observed a significant mean (SD) increase in the activation marker of CD154⁺ T cells (0.17% [0.047^%]) in patients with EoE-A compared with control patients (0.034% [0.007%]) and EoE-I (0.025% [0.008]). These CD4⁺ T cells expressed significantly increase levels of T_H2 cytokines (interleukins 4, 5, and 13) compared with the EoE-I and control groups. CD3⁺CD4⁺CD154⁺IL-5⁺ cells were significantly increased by milk antigens in both milk-induced EoE-A (0.050% [0.008%] to 0.079% [0.017%]) and EoE-I (0.0045% [0.002%] to 0.014% [0.008%]) compared with the controls (0.008% [0.003%] to 0.003% [0.001%]).

Conclusion: Our findings indicate that in EoE peripheral T cells have specific activation to milk allergens.