Citation

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Dietary protein shapes the profile and repertoire of intestinal CD4 + T cells

Lockhart, A;Reed, A;de Castro, TR;Herman, C;Canesso, MCC;Mucida, D;

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.