Abstract
The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4 (+) T cells. Combining antigenically defined diets with gnotobiotic models, we show that food and microbiota distinctly influence the profile and T cell receptor repertoire of intestinal CD4 (+) T cells. Independent of the microbiota, dietary proteins contributed to accumulation and clonal selection of antigen-experienced CD4 (+) T cells at the intestinal epithelium, imprinting a tissue specialized transcriptional program including cytotoxic genes on both conventional and regulatory CD4 (+) T cells (Tregs). This steady state CD4 (+) T cell response to food was disrupted by inflammatory challenge, and protection against food allergy in this context was associated with Treg clonal expansion and decreased pro-inflammatory gene expression. Finally, we identified both steady state epithelium-adapted CD4 (+) T cells and tolerance-induced Tregs that recognize dietary antigens, suggesting that both cell types may be critical for preventing inappropriate immune responses to food.