Pathogenesis of Sjögren's syndrome-like autoimmune lesions in MRL/lpr mice.
Sjögren's syndrome in humans is a chronic inflammatory disease with a presumed autoimmune etiology of the exocrine organs, involving in particular the salivary and lacrimal glands. The pathogenesis of this syndrome remains unclear, but the majority of infiltrating cells in the salivary glands are CD4+ T cells both in humans and rodents. Since many cytokines are involved in the development of T cell-mediated autoimmunity, local cytokine gene expression was analyzed in vivo using an animal model for Sjögren's syndrome in MRL/lpr mice. Overexpression of interleukin-1 (IL-1)beta and tumour necrosis factor (TNF) was detected before the onset of inflammatory lesions in the salivary gland, and the upregulation of IL-6 mRNA was also found in accordance with autoimmune sialadenitis in MRL/lpr mice. The inflammatory cytokines such as IL-1 beta, TNF, and IL-6 have proved to play important roles as regulatory proteins inducing autoimmune phenomena. In addition, the expression of T cell antigen receptor beta (TCR) beta transcripts in the salivary gland tissues was analyzed. Transcript for V beta 8 was predominantly detected in the T cells infiltrating sialadenitis from the onset of the disease, suggesting that CD4+ T cells bearing TCR V beta 8 play an essential role in recognizing unknown autopeptide in the autoimmune sialadenitis of MRL/lpr mice. Furthermore, Sjögren's syndrome-like autoimmune lesions were successfully transferred into severe combined immunodeficiency (SCID) mice, and these lesions were prevented by administration of anti-CD4, and anti-V beta 8 monoclonal antibodies. This article will review recent observations of these pathogenetic analyses of autoimmune sialadenitis as it occurs in MRL/lpr mice.
Hayashi
Y
Y
Department of Oral Pathology, School of Dentistry, University of Tokushima, Japan.
Haneji
N
N
Hamano
H
H
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D016219:Immunotherapy, Adoptive; D051379:Mice; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012469:Salivary Glands / Q000276:immunology; D012793:Sialadenitis / Q000235:genetics / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell