Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Upcoming)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Intestinal development and homeostasis require activation and apoptosis of diet-reactive T cells
Alexander Visekruna, … , Krishnaraj Rajalingam, Ulrich Steinhoff
Alexander Visekruna, … , Krishnaraj Rajalingam, Ulrich Steinhoff
Published April 2, 2019
Citation Information: J Clin Invest. 2019;129(5):1972-1983. https://doi.org/10.1172/JCI98929.
View: Text | PDF
Research Article Gastroenterology Immunology

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

  • Text
  • PDF
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.

Authors

Alexander Visekruna, Sabrina Hartmann, Yasmina Rodriguez Sillke, Rainer Glauben, Florence Fischer, Hartmann Raifer, Hans Mollenkopf, Wilhelm Bertrams, Bernd Schmeck, Matthias Klein, Axel Pagenstecher, Michael Lohoff, Ralf Jacob, Oliver Pabst, Paul William Bland, Maik Luu, Rossana Romero, Britta Siegmund, Krishnaraj Rajalingam, Ulrich Steinhoff

×

Figure 1

Helios+Foxp3–CD4+ T cells accumulate in Peyer patches.

Options: View larger image (or click on image) Download as PowerPoint
Helios+Foxp3–CD4+ T cells accumulate in Peyer patches.
(A) Percentage of...
(A) Percentage of CD44+CD62L–CD4+ T cells in spleen, mLNs, inguinal lymph nodes (iLNs), PPs, siLP, and cLP of SPF and GF mice (n = 6, 1 of 2 experiments is shown). (B) Representative dot plots of CD4+ T cells from SPF mice expressing Helios and Foxp3 in indicated organs (n = 6). (C) Expression of Helios and Foxp3 on gated CD4+ T cells of PPs from GF mice (n = 5). (D) Distribution of Helios+Foxp3–CD4+ T cells in indicated tissues of SPF and GF mice (n = 6, 1 of 2 experiments is shown). (E) Expression of Helios, CD62L, CD44, and CD69 in PP CD4+ T cells from SPF mice (n = 6). (F) TCR Vβ repertoire of Helios+Foxp3–CD4+ T cells (white) and Tregs (black) derived from PPs of SPF mice (n = 5, 1 of 2 experiments is shown). (G) Analysis of CD25, CTLA-4, and IL-10 in Helios+Foxp3–CD4+ T cells (red) and Tregs (black) from PPs of SPF mice (n = 3). (H) In vitro suppression assay of CD4+ T responder cells (Teff) in the presence of in vitro–generated Tregs or CD44+CD62L–Helios+Foxp3–CD4+ T cells (THel) enriched from PPs of DEREG mice. Data are representative of 2 (A–D and F) or 3 (E, G, and H) independent experiments. Error bars indicate mean ± SD. Data were analyzed using the Student’s t test; *P < 0.05, ***P < 0.001.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts