Accelerated onset of age-related autoimmune lesions in MRL/+ mice by ovariectomy.
MRL/Mp +/+ (MRL/+) mice, not bearing the lpr gene, are known to have age-related autoimmune lesions in several organs such as pancreas, salivary and lacrimal glands at 30-weeks-old or more. In this study, MRL/+ mice were ovariectomized at 4-weeks-old, and their natural histories were analysed. Ovariectomy (Ovx) of MRL/+ mice led to marked acceleration of organ-specific autoimmune lesions exclusively in the salivary and lacrimal glands at 8-weeks-old or more, whereas no significant inflammatory change was observed in the pancreas. In the vast majority of inflammatory infiltrates, CD3+ CD4+ T cells were predominant in both the salivary and lacrimal glands of Ovx-MRL/+ mice. Up-regulated expression of cytokine genes including IL-1 beta, TNF-alpha, IL-2, interferon (IFN)-gamma, and IL-6 was detected in the salivary gland of Ovx-MRL/+ mice by reverse transcriptase (RT)-PCR analysis. FACS analysis of spleen cells of Ovx-mice revealed increase in I-Ak expression on B220+ cells, and autoantibody production against the salivary gland-specific antigen in sera from Ovx-MRL/+ mice, but not in control mice. These results suggest that age-related autoimmunity in the salivary and lacrimal glands were accelerated in Ovx-MRL/+ mice, and that autoreactive Th1 cells were activated associated with organ-specific autoantibody production.
Ishimaru
N
N
Department of Pathology, Tokushima University School of Dentistry, Japan.
Haneji
N
N
Hamano
H
H
Kumiko
Y
Y
Takahashi
M
M
Hayashi
Y
Y
D000375:Aging / Q000276:immunology*; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D015139:Blotting, Southern; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D010052:Ovariectomy; D016133:Polymerase Chain Reaction
D016207:Cytokines