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J Clin Invest. 2019 Apr 2;130:1972-1983. doi: 10.1172/JCI98929. eCollection 2019 Apr 2.

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

Author information

1
Institute for Medical Microbiology and Hospital Hygiene, Philipps University of Marburg, Germany.
2
Medical Department for Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
3
Flow Cytometry Core Facility, Philipps University Marburg, Germany.
4
Max Planck Institute for Infection Biology, Core Facility Microarray/Genomics, Berlin, Germany.
5
Institute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Philipps University Marburg, Germany.
6
Institute for Immunology, University Medical Center, Mainz, Germany.
7
Department of Neuropathology, Philipps University of Marburg, Germany.
8
Department of Cell Biology and Cell Pathology, Philipps University of Marburg, Germany.
9
Institute of Molecular Medicine, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany.
10
Department of Microbiology & Immunology, Gothenburg University, Gothenburg, Sweden.
11
Cell Biology Unit, University Medical Center, Mainz, Germany.

Abstract

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

PMID:
30939122
PMCID:
PMC6486345
[Available on 2019-08-01]
DOI:
10.1172/JCI98929
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