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

M Rįki, S Tollefsen, Ų Molberg, KEA Lundin, LM Sollid… - Gastroenterology, 2006 - Elsevier
M Rįki, S Tollefsen, Ų Molberg, KEA Lundin, LM Sollid, FL Jahnsen
Gastroenterology, 2006Elsevier
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 …
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.
Elsevier