Scientists at the University of Minnesota School of Medicine have solved the mystery of why most people don’t develop an immune response after every meal. The results of the study, published in the journal Nature, showed that foreign proteins in food provoke the formation of regulatory immune cells that suppress serious inflammatory responses.

To explain the paradoxical tolerance of the immune system to food, experts conducted experiments with mice that grew up on a gluten-free diet, after which they were given different foods and analyzed subsequent immune responses. Some of the foods contained one or more types of gluten proteins known as gliadins. People with dietary celiac disease develop gluten intolerance precisely because of a defective immune response.

In most people, food does not lead to the development of a T-cell immune response, despite the fact that they consume about a hundred grams of foreign plant and animal proteins every day. However, the same reactions occur in the body that cause an immune response against the proteins of viruses and bacteria. Dietary proteins are presented by major histocompatibility complex class II (MHCII) CD4+ T cells, which usually recognize foreign molecules for a future attack on the pathogen. In the fight against infection, T cells provoke an inflammatory response, which is absent in the case of dietary proteins.

The researchers found that in rodents after gliadin, there was only a slight increase in the number of protein-specific T cells in the lymphoid organs of the gastrointestinal tract. Intensive proliferation of pro-inflammatory CD4+ cells was suppressed by another type of immune cells, regulatory Treg cells. Some gliadin-specific T cells then turned into follicular helper T cells, which elicited a weak antibody response. A full-fledged immune response did not develop because many of the T cells that were able to proliferate turned out to be non-canonical, that is, unable to cause inflammation, and, in the end, turned into Treg themselves.

Thus, exposure of naïve T cells to dietary antigens leads to the development of T cell subpopulations that are unable to induce inflammatory functions and yet produce T cells that suppress inflammation.