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