Egg allergen-specific T-cell and cytokine responses in healthy and egg-allergic children naturally tolerating baked egg

Abstract

Background: Type 1 regulatory T (Tr1) cells are critical players in maintaining peripheral tolerance, by producing high IL-10 levels in association with inducible T-cell co-stimulator (ICOS) expression. Whether these cells play a role in naturally acquired baked egg tolerance is unknown. Objectives: Evaluate frequencies of egg-responsive Tr1 and Th2 cells in egg-allergic children that naturally acquired baked egg tolerance (BET) versus non-egg-allergic (NEA) children. Methods: Peripheral blood mononuclear cells from 70 natural BET and 15 NEA children were stimulated for 7 days with ovalbumin and ovomucoid. By flowcytometry, egg-responsive Tr1 cells were identified by co-expression of CD49b and LAG3, and Th2 cells by expression of CD49b but absence of LAG3. Seven-day cultured supernatant was analyzed for Th1, Th2, Tr1, and Th17 cytokines by MSD. Results: Natural BET children had a higher percentage of egg-responsive Th2 cells vs. NEA children (6.75% vs. 10.35%, p = .006). No significant difference was found in frequencies of egg-responsive Tr1 cells between NEA and natural BET children (11.40% vs. 12.55%, p = .42), although Tr1-related IL-10 and IL-21 production was higher in BET children. Interestingly, egg-responsive Tr1 cells from NEA children expressed higher ICOS levels vs. natural BET children (97.90 vs. 88.20, p < .0001). Supernatant from natural BET children showed elevated levels of Th2 cytokines IL-5, IL-9 and IL-13 and Th17 cytokine IL-17A. Conclusion: Natural BET children maintain increased egg-specific Th2 responses, along with comparable proportions of egg-responsive Tr1 cells exhibiting higher IL-10 but lower ICOS expression in comparison with NEA children.