A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells

Gastroenterology. 2006 Aug;131(2):428-38. doi: 10.1053/j.gastro.2006.06.002.


Background & aims: Celiac disease is a chronic inflammation of the duodenal mucosa driven by gluten-reactive T cells restricted by the disease-associated HLA-DQ2 molecule. The mechanisms that regulate the activation of mucosal T cells are, however, understood poorly. The aim of this study was to identify the antigen-presenting cells that are responsible for the activation of gluten-reactive T cells in the celiac lesion.

Methods: Intestinal biopsy specimens obtained from untreated and treated celiac patients and normal controls were either snap-frozen directly or incubated for 24 hours with or without gluten peptides. Cryosections were subjected to multicolor immunofluorescence applying monoclonal antibodies to a range of antigen-presenting cell markers. Macrophages and dendritic cells were isolated from enzymatically digested small intestinal biopsies of untreated patients and incubated with gluten-reactive T-cell clones to measure their antigen-presenting capacity.

Results: HLA-DQ2+ cells in the normal duodenal mucosa consisted of 2 distinct cell populations: about 80% were CD68+ DC-lysosome intercellular adhesion molecule-3-grabbing nonintegrin+ macrophages and 20% were CD11c+ dendritic cells. Importantly, the CD11c+ dendritic cells accumulated in the celiac lesion and revealed an activated phenotype expressing CD86 and DC-specific-associated membrane protein. Moreover, when isolated from challenged biopsy specimens, the CD11c+ dendritic cells efficiently activated gluten-reactive T cells.

Conclusions: Our results suggest that a unique subset of dendritic cells are responsible for local activation of gluten-reactive T cells in the celiac lesion.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Biopsy
  • CD11 Antigens / immunology
  • Celiac Disease / immunology
  • Celiac Disease / pathology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Duodenum / pathology*
  • Glutens / pharmacology*
  • HLA-DQ Antigens / immunology*
  • Humans
  • In Vitro Techniques
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology*
  • Lymphocyte Activation / immunology*
  • Middle Aged
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD11 Antigens
  • CD68 antigen, human
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • Glutens