Food-sensitized pediatric patients show colonic cow's milk protein-specific Th2 cells

Background: Manifestations of food allergies vary among patients, being the most common gastrointestinal, skin and respiratory symptoms. This study aimed to identify and characterize polyp Th2 cells as a critical component of the allergic reaction. We previously characterized colorectal polyps in patients sensitized to food allergens as inflammatory, with a Type 2-dominated stroma, with elevated IL-13, IL-4 and locally synthesized IgE. Methods: We isolated milk-specific T cells from tissue and blood of food-sensitized patients (n=10) and obtained cell lines and cell clones. Proliferation, specificity, cytokine secretion, gut homing markers and TCR nature were analyzed after antigen recall; CCL25 was assessed in polyps and surrounding tissue. Results: Lamina propria and peripheral T cells responded similarly to cow´s milk proteins, showing similar cell proliferation index and Th2 cytokine release in vitro. All CD4 T cells expressed the membrane T receptor and secreted higher IL-13 amounts than unstimulated cells, whereas IFN-γ secretion remained unchanged. Remarkably, the gut homing chemokine receptor CCR9 was augmented in cow’s milk-specific peripheral and lamina propria T cells, and CCL25 was found to be expressed in the inflammatory polyp tissue and not in the adjacent mucosa. Conclusion: We isolated and characterized cow´s milk-specific lamina propria CD4 TCRαβ Th2 cells from colonic inflammatory polyps. The CCR9 expression on polyp cells and the increased production of tissue CCL25 might facilitate T cells’ recruitment, which are key players in the allergic reaction to promote local IgE synthesis. Our findings may be critical to proposing rational and novel T cell-targeted immunotherapies.