Intestinal development and homeostasis require activation and apoptosis of diet-reactive T cells

J Clin Invest. 2019 Apr 2;129(5):1972-1983. doi: 10.1172/JCI98929.


The impact of food antigens on intestinal homeostasis and immune function is poorly understood. Here, we explored the impact of dietary antigens on the phenotype and fate of intestinal T cells. Physiological uptake of dietary proteins generated a highly activated CD44+Helios+CD4+ T cell population predominantly in Peyer patches. These cells are distinct from regulatory T cells and develop independently of the microbiota. Alimentation with a protein-free, elemental diet led to an atrophic small intestine with low numbers of activated T cells, including Tfh cells and decreased amounts of intestinal IgA and IL-10. Food-activated CD44+Helios+CD4+ T cells in the Peyer patches are controlled by the immune checkpoint molecule PD-1. Blocking the PD-1 pathway rescued these T cells from apoptosis and triggered proinflammatory cytokine production, which in IL-10-deficient mice was associated with intestinal inflammation. In support of these findings, our study of patients with Crohn's disease revealed significantly reduced frequencies of apoptotic CD4+ T cells in Peyer patches as compared with healthy controls. These results suggest that apoptosis of diet-activated T cells is a hallmark of the healthy intestine.

Keywords: Gastroenterology; Homeostasis; Immunology; Inflammatory bowel disease; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Biopsy
  • CD4-Positive T-Lymphocytes / cytology*
  • Diet*
  • Enzyme-Linked Immunosorbent Assay
  • Homeostasis
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunoglobulin A / metabolism
  • Interleukin-10 / metabolism
  • Intestine, Small / cytology*
  • Intestine, Small / metabolism
  • Intestine, Small / pathology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Peyer's Patches / cytology


  • CD44 protein, human
  • Hyaluronan Receptors
  • IL10 protein, human
  • IL10 protein, mouse
  • Immunoglobulin A
  • Interleukin-10