Mechanism of the development of autoimmune dacryodenitis in the mouse model for primary Sjögren's syndrome.
To elucidate the mechanism of development in autoimmune lacrimal gland disease, we analyzed different aspects of autoimmune dacryoadenitis in a newly established mouse model for primary Sjögren's syndrome, focusing on the local expressions of cytokine genes, and the repertoire of T cell receptor (TCR) V beta genes transcribed within the inflammatory infiltration in the lacrimal glands. We found that the vast majority of inflammatory infiltration into the lacrimal glands were CD4+ V beta 8+ T cells. We detected the up-regulation of local cytokine genes (IL-1 beta, TNF-alpha, IL-2, IFN-gamma, IL-10, IL-12p40) in the lacrimal glands with very early inflammatory lesions by reverse transcriptase (RT)-PCR analysis. The predominant expression of the V beta 8 gene segment was detected from a very early stage, while extensive age-related diversity of TCR V beta gene usage was observed. Single-strand conformation polymorphism (SSCP) analysis demonstrated a distinct and a common binding pattern in the PCR product of the V beta 8 gene on the infiltrating cells during the course of the disease. These data suggest that in autoimmune dacryoadenitis of the mouse model for primary Sjögren's syndrome there may be a restricted usage of TCR V beta elements on a very early stage of the autoimmune lesion to recognize unknown self-antigen, and the autoreactive CD4+ T cells constitute a unique cytokine profile in the autoimmune lacrimal gland disease.
Takahashi
M
M
Department of Ophthalmology, School of Medicine, University of Tokushima, Japan.
Mimura
Y
Y
Hamano
H
H
Haneji
N
N
Yanagi
K
K
Hayashi
Y
Y
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics; D003607:Dacryocystitis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta