Escherichiacoli-Specific CD4+ T Cells Have Public T-Cell Receptors and Low Interleukin 10 Production in Crohn's Disease

Cell Mol Gastroenterol Hepatol. 2020;10(3):507-526. doi: 10.1016/j.jcmgh.2020.04.013. Epub 2020 May 1.


Background & aims: Crohn's disease (CD) likely represents decreased immune tolerance to intestinal bacterial antigens. Most CD patients have high titers of antibodies to intestinal commensal proteins, including the outer membrane porin C (OmpC) of Escherichia coli.

Methods: By using major histocompatibility complex II tetramers, we identified an HLA-DRB1∗15:01-restricted peptide epitope of OmpC recognized by CD4+ T cells in peripheral blood mononuclear cells from HLA-DRB1∗15:01+ healthy control (HC) and CD patients.

Results: The precursor frequency of these cells in CD correlated with anti-OmpC IgA titers, but did not differ from that of HCs. In both cohorts, they showed a CD161+, integrin α4β7+ phenotype ex vivo by flow cytometry, distinct from the C-X-C Motif Chemokine Receptor 3 phenotype of autologous influenza hemagglutinin (Flu) peptide-specific T cells. The T-cell receptor α and β chains of in vitro-expanded OmpC-specific T-cell clones often contained public amino acid sequences that were identical in cells from different patients. Expanded T-cell clones from CD subjects produced significantly less interleukin (IL)10 (P < .0001) than those from HCs, and a trend toward decreased production of the T helper 2 cell-associated IL4, IL5, and IL13 by CD clones also was seen.

Conclusions: Both HCs and CD patients have detectable OmpC-specific T cells in circulation, with similar immunophenotypes and often identical T-cell-receptor sequences. However, expanded clones from patients with CD produce less of the immunoregulatory cytokine IL10, showing a selective defect in the regulatory function of intestinal microbial antigen-specific T cells in patients with CD.

Keywords: IL10; OmpC; Public TCR; Tetramer-Guided Epitope Mapping.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Crohn Disease / blood
  • Crohn Disease / immunology*
  • Crohn Disease / microbiology
  • Epitopes, T-Lymphocyte / immunology
  • Escherichia coli / immunology
  • Escherichia coli Proteins / immunology*
  • Female
  • Gastrointestinal Microbiome / immunology*
  • HLA-DRB1 Chains / metabolism
  • Healthy Volunteers
  • Host Microbial Interactions / immunology
  • Humans
  • Interleukin-10 / metabolism
  • Male
  • Middle Aged
  • Porins / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Young Adult


  • Epitopes, T-Lymphocyte
  • Escherichia coli Proteins
  • HLA-DRB1 Chains
  • HLA-DRB1*15:01 antigen
  • IL10 protein, human
  • OmpC protein
  • Porins
  • Receptors, Antigen, T-Cell
  • Interleukin-10