A population of suppressive T cells in the small intestines of mice prevents immune responses to solid foods, a new study finds. Why our immune system, which so effectively attacks foreign microbes, doesn't attack the molecules in the food we eat is a longstanding mystery, but now, results by Kwang Soon Kim et al. provide new insights. The team created a group of mice that were raised on a chemical diet completely lacking macromolecules from solid foods, meaning these mice never had dietary antigens in their guts. These antigen-free (AF) mice were compared to mice fed regular solid foods, including to germ-free (GF) mice that lack gut microbes. While GF mice had peripheral Treg (pTreg) cells in the small intestines, AF mice did not. This suggests that dietary antigens induce development of most pTreg cells in the small intestines. Indeed, when adult GF mice were placed on the antigen-free diet, the fraction of pTreg cells within the small intestines decreased considerably, by about 40% after four weeks. These results indicate that pTreg cells in the small intestines are continuously generated and replaced in response to dietary antigens, the authors say. In subsequent experiments, mice that were introduced to an antigen-free diet, driving a severe reduction of pTreg cells in their small intestines, were fed proteins from chicken eggs. Within two weeks these mice experienced a higher incidence and severity of diarrhea. Collectively, these results suggest that pTreg cells in the small intestines play a key role in determining how our immune system handles the foods we eat.