A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells.
Gastroenterology
; 131(2): 428-38, 2006 Aug.
Article
em En
| MEDLINE
| ID: mdl-16890596
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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Ativação Linfocitária
/
Linfócitos T
/
Antígenos HLA-DQ
/
Duodeno
/
Glutens
/
Mucosa Intestinal
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Humans
/
Middle aged
Idioma:
En
Revista:
Gastroenterology
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Noruega