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A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells.
Gastroenterology. 2006 Aug; 131(2):428-38.G

Abstract

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.

Authors+Show Affiliations

Institute of Immunology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. melinda.raki@medisin.uio.noNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16890596

Citation

Ráki, Melinda, et al. "A Unique Dendritic Cell Subset Accumulates in the Celiac Lesion and Efficiently Activates Gluten-reactive T Cells." Gastroenterology, vol. 131, no. 2, 2006, pp. 428-38.
Ráki M, Tollefsen S, Molberg Ø, et al. A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells. Gastroenterology. 2006;131(2):428-38.
Ráki, M., Tollefsen, S., Molberg, Ø., Lundin, K. E., Sollid, L. M., & Jahnsen, F. L. (2006). A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells. Gastroenterology, 131(2), 428-38.
Ráki M, et al. A Unique Dendritic Cell Subset Accumulates in the Celiac Lesion and Efficiently Activates Gluten-reactive T Cells. Gastroenterology. 2006;131(2):428-38. PubMed PMID: 16890596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells. AU - Ráki,Melinda, AU - Tollefsen,Stig, AU - Molberg,Øyvind, AU - Lundin,Knut E A, AU - Sollid,Ludvig M, AU - Jahnsen,Frode L, PY - 2006/01/23/received PY - 2006/05/11/accepted PY - 2006/8/8/pubmed PY - 2006/9/20/medline PY - 2006/8/8/entrez SP - 428 EP - 38 JF - Gastroenterology JO - Gastroenterology VL - 131 IS - 2 N2 - 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. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/16890596/A_unique_dendritic_cell_subset_accumulates_in_the_celiac_lesion_and_efficiently_activates_gluten_reactive_T_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(06)01231-5 DB - PRIME DP - Unbound Medicine ER -