J. Clin. Invest. 129, 1972–1983 (2019)

The gut is continually exposed to dietary antigens, but how tolerance is maintained in the face of this potential stimulus is still not entirely clear. In the Journal of Clinical Investigation, Steinhoff and colleagues look at the fate of T cells in the Peyer’s patches of normal mice. A conventional diet results in the microbiome-independent accumulation of distinctive Helios+Foxp3– CD4+ T cells that are non-suppressive and have apoptotic and exhausted signatures. Generation of Helios+Foxp3– CD4+ T cells in the Peyer’s patches requires stimulation via the T cell antigen receptor, and mice fed an elemental, antigen-free diet have fewer of these cells. Efferocytosis of Helios+Foxp3– CD4+ T cells by macrophages results in their production of the cytokine IL-10. These findings suggest that food antigens trigger T cell death in the small intestine, which enforces a tolerogenic response.