Effector mechanism of experimental autoimmune sialadenitis in the mouse model for primary Sjögren's syndrome.
We have recently established a new animal model for primary Sjögren's syndrome in NFS/sld mutant mice thymectomized 3 days after birth (3dTX) bearing an autosomal recessive gene with sublingual gland differentiation arrest. In this study, we analyze developing mechanisms of experimental autoimmune sialadenitis (EAS) in the mouse model, focusing on local expressions of cytokine and cell adhesion molecule genes by reverse transcriptase-polymeric chain reaction (RT-PCR) and immunohistochemistry, kinetic analysis of splenic lymphocytes expressing activation markers, and I-Aq class-II molecules by flow cytometry (FACS). We found up-regulation of local cytokine genes (IL-1 beta, TNF-alpha, IL-2, IFN-gamma, IL-6, IL-10, IL-12p40) and cell adhesion molecule genes (ICAM-1, LFA-1, CD44, Mel-14) in the salivary glands from mice with EAS by RT-PCR, which were supported by immunohistochemistry. FACS analysis demonstrated that a significant proportion of splenic CD4+ T cells express activation markers (CD44, LFA-1, Mel-14low, CD45RB(low)) at a high level and an increase in expression of B220+ B cells bearing I-Aq class-II molecules. These data suggest that spontaneous EAS in 3dTX NFS/sld mutant mice may be triggered by an in situ activation of autoreactive CD4+ T cells comprising unique cytokine profile (high levels of IL-2, IFN-gamma, IL-10, and IL-12p40 mRNA) in the salivary glands.
Hayashi
Y
Y
Department of Pathology, Tokushima University School of Dentistry, Japan.
Haneji
N
N
Hamano
H
H
Yanagi
K
K
Takahashi
M
M
Ishimaru
N
N
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology; D012793:Sialadenitis / Q000276:immunology* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D018836:Inflammation Mediators