HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22

Mucosal Immunol. 2010 Nov;3(6):594-601. doi: 10.1038/mi.2010.36. Epub 2010 Jun 23.

Abstract

We have analyzed the production of the effector cytokines interleukin (IL)-17, IL-21, and IL-22 in gluten-reactive CD4(+) T cells of celiac disease patients, either cultured from small intestinal biopsies or isolated from peripheral blood after an oral gluten challenge. Combining intracellular cytokine staining with DQ2-α-II gliadin peptide tetramer staining of intestinal polyclonal T-cell lines, we found that gluten-specific T cells produced interferon-γ (IFN-γ) and IL-21, but not IL-17 or IL-22, even if other T cells of the same lines produced these cytokines. Similarly, in DQ2-α-II-specific T cells in peripheral blood of gluten-challenged patients, very few stained for intracellular IL-17, whereas many cells stained for IFN-γ. We conclude that gluten-reactive T cells produce IL-21 and IFN-γ, but not IL-17. Their production of IL-21 suggests a role for this cytokine in the pathogenesis of celiac disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Celiac Disease / immunology*
  • Cell Line
  • Gliadin / immunology
  • Gliadin / metabolism*
  • Glutens / immunology
  • HLA-DQ Antigens / immunology
  • HLA-DQ Antigens / metabolism*
  • Humans
  • Interleukin-17 / metabolism
  • Interleukin-22
  • Interleukins / metabolism*
  • Intestines / immunology
  • Intestines / pathology
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism

Substances

  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • Interleukin-17
  • Interleukins
  • Peptide Fragments
  • Glutens
  • Gliadin
  • interleukin-21