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.