Immune tolerance of food is mediated by multiple layers of CD4+ T cell dysfunction

ABSTRACT: Gastrointestinal health depends on the adaptive immune system tolerating the foreign proteins in food1,2. This tolerance is paradoxical because the immune system normally attacks foreign substances by generating inflammation. Here, we addressed this conundrum by using a sensitive cell enrichment method to assess how CD4+ helper T cells respond to peptides from food. Polyclonal CD4+ T cells responded to food peptides, including a natural one from gliadin, by proliferating weakly in secondary lymphoid organs of the gut-liver axis due to the action of regulatory T cells. A few food-specific T cells then differentiated into T follicular helper cells that promoted a weak antibody response. Most cells, however, lacked T helper lineage markers and became either naïve-like or T follicular helper-like anergic cells both with limited capacity to migrate to the lamina propria and form Th1 cells. Eventually, many of the T helper lineage-negative cells became Treg cells themselves via an IL-2-dependent mechanism. Our results indicate that food peptide-specific CD4+ T cells do not cause immunopathology because they are activated in a Treg cell-generated environment to become hyporesponsive cells that do not drive inflammation and are prone to become peripheral Treg cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE202423 | GEO | 2022/05/31

REPOSITORIES: GEO