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 havepreviously characterized colorectal polyps in patients sensitized to food allergens. These polyps are classified as inflammatory andpresent a T helper 2 (Th2) environment, with elevated interleukin (IL)-13 and IL-4, and are a site of immunoglobulin E synthesis. Inthis study, we characterized and isolated cow’s milk protein–specific T cell lines and T cell clones from the lamina propria of polypsfrom 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 andexpressed the membrane TCRαβ receptor and secreted higher IL-4, IL-5, and IL-13 amounts than unstimulated cells, whereasinterferon 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 theadjacent mucosa. In conclusion, we isolated and characterized cow’s milk–specific lamina propria CD4+ Th2 cells from colonicinflammatory polyps. CCR9 expression on these cells, along with increase secretion of CCL25 in the polyp, favors recruitment andcow’s milk–specific allergic response within the inflammatory polyp tissue. Our findings may be critical to understand the underlyingmechanism that promotes immunoglobulin E synthesis in the colon of cow’s milk proteins allergic patients, contributing to thedevelopment of novel T cell–targeted immunotherapies.