Cytokines, Adhesion Molecules, and Immune Deviation in Autoimmune Salivary Gland Disease

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The immunopathology of most autoimmune diseases has been well defined, but the mechanisms responsible for the breakdown of self-tolerance and which lead to the development of autoimmune lesions are still unclear. Primary SjÖgren's syndrome in humans is known to be an autoimmune disease characterized by diffuse lymphoid cell infiltration in 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 were CD4+ T cells both in humans and rodents. Since many cytokines and adhesion molecules are involved in the development of T cell-mediated autoimmunity, we have investigated local cytokine, and adhesion molecule gene expression using animal model for primary SjÖgren's syndrome in MRL/lpr, and NFS/sld mice. Overexpression of interleukin-l(IL-1) β and tumor necrosis factor(TNF)-α, interferon(IFN)-γ, IL-6, IL-10, IL-12(p40) was detected in the salivary gland, and the up-regulation of ICAM-1, LFA-1, CD44, Mel-14 mRNA was found in accordance with autoimmune sialadenitis. In addition, we have analysed the expressionn of T cell antigen receptor(TCR)V β transcripts in the salivary gland tissues. Transcript for V β 8 was predominantly detected in the T cell infiltrating sialadenitis from the onset of the disease, suggesting that CD4+ T cells bearing TCR V β 8 are play essential roles to recognize unknown autopeptide in the autoimmune salivary gland disease.

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