A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells.
OBJECTIVE
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.
Ráki
Melinda
M
Institute of Immunology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. melinda.raki@medisin.uio.no
Tollefsen
Stig
S
Molberg
Øyvind
Ø
Lundin
Knut E A
KE
Sollid
Ludvig M
LM
Jahnsen
Frode L
FL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001706:Biopsy; D018845:CD11 Antigens / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004386:Duodenum / Q000473:pathology*; D005983:Glutens / Q000494:pharmacology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018845:CD11 Antigens; D005983:Glutens; D006683:HLA-DQ Antigens; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C053186:HLA-DQ2 antigen