Localization and characterization of antigen-presenting dendritic cells in the gastric mucosa of murine and human autoimmune gastritis.
BACKGROUND
Activated CD4+ T cells and inflammatory cytokines are implicated in the pathogenesis of experimental autoimmune gastritis. However, there is a paucity of information about the cells that induce them. Antigen-presenting dendritic cells (DCs) play a cardinal role in the formation and survival of activated lymphocytes.


METHODS
Autoimmune gastritis was induced in neonatal BALB/c mice by thymectomy. DCs were detected in situ in the gastric mucosa from thymectomized mice and in patients with autoimmune gastritis, by immunohistochemistry and immunoelectron microscopy. The expression of MHC class II and CD86 antigens on DCs in the gastric mucosa and spleen was evaluated in dual-colour flow cytometry.


RESULTS
DCs were detected in the gastric mucosa of mice with autoimmune gastritis, and the number of DCs increased as the levels of gastritis became more severe as time passed following thymectomy. Flow cytometric analyses revealed that more than 60% of the DCs in the gastric mucosa had a mature phenotype (expressed MHC class II and/or CD86 antigens) both at 4 and 16 weeks after thymectomy. Activated and mature DCs were localized in the gastric mucosa from patients with autoimmune gastritis.


CONCLUSIONS
This is the first report on the localization and phenotypes of DCs in the gastric mucosa of autoimmune gastritis. The presence of mature DCs in the gastric mucosa of murine and human autoimmune gastritis, in spite of their absence in the gastric mucosa of normal mice, suggests that mature DCs play a role in the pathogenesis of autoimmune gastritis.
Ninomiya
T
T
Ehime University School of Medicine, Shigenobu-Cho, Ehime, Japan.
Matsui
H
H
Akbar
S M
SM
Murakami
H
H
Onji
M
M
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D051940:B7-2 Antigen; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D005753:Gastric Mucosa / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D005756:Gastritis / Q000276:immunology* / Q000473:pathology; D006681:HLA-D Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D013934:Thymectomy
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D006681:HLA-D Antigens; D000949:Histocompatibility Antigens Class II; D016167:Integrin alphaXbeta2; D008562:Membrane Glycoproteins