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

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 proinflammatory 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. Lockhart et al. demonstrate that exposure to food protein drives an antigen-specific CD4(+) T cell response characterized at steady state by accumulation at the intestinal epithelium and tissue-specialized transcriptional imprinting. This process is disrupted upon either allergic sensitization or tolerance.

Automated summary

The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4(+) T cells. Combining antigenically defined diets with gnotobiotic models, the study shows that both food and microbiota have distinct effects on the profile and T cell receptor repertoire of intestinal CD4(+) T cells. The response of CD4(+) T cells to food is disrupted by inflammatory challenge, but protection against food allergy is associated with Treg clonal expansion and decreased proinflammatory gene expression.