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

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 celis 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 DG-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.