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

Abstract

Food allergies have become a health concern worldwide. Around 6% to 10% of children are allergic to cow's milk proteins. We have previously characterized colorectal polyps in patients sensitized to food allergens. These polyps are classified as inflammatory and present a type 2 environment, with elevated interleukin (IL)-13 and IL-4, and are a site of immunoglobulin E synthesis. In this study, we characterized and isolated cow's milk protein-specific T cell lines and T cell clones from the lamina propria of polyps from patients sensitized to these proteins. Isolated T cells responded to cow's milk proteins similarly to peripheral blood T cells, showing antigen-specific cell proliferation and Th2 cytokines release in vitro. T cell clones obtained were all CD4+ T cells and expressed the membrane TCRαβ receptor and secreted higher IL-4, IL-5, and IL-13 amounts than unstimulated cells, whereas interferon 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. In conclusion, we isolated and characterized cow's milk-specific lamina propria CD4+ Th2 cells from colonic inflammatory polyps. CCR9 expression on these cells, along with increase secretion of CCL25 in the polyp, favors recruitment and cow's milk-specific allergic response within the inflammatory polyp tissue. Our findings may be critical to understand the underlying mechanism that promotes immunoglobulin E synthesis in the colon of cow's milk proteins allergic patients, contributing to the development of novel T cell-targeted immunotherapies.

Keywords: T lymphocytes; allergy; colorectal polyps; cow's milk proteins.