Hayashi Y, Haneji N, Hamano H
Department of Oral Pathology, School of Dentistry, University of Tokushima, Japan.
Pathol Int. 1994 Aug;44(8):559-68. doi: 10.1111/j.1440-1827.1994.tb01716.x.
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.
人类干燥综合征是一种慢性炎症性疾病，外分泌器官可能存在自身免疫病因，尤其累及唾液腺和泪腺。该综合征的发病机制尚不清楚，但在人类和啮齿动物中，唾液腺中大多数浸润细胞都是CD4 + T细胞。由于许多细胞因子参与T细胞介导的自身免疫发展，因此使用MRL/lpr小鼠干燥综合征动物模型在体内分析了局部细胞因子基因表达。在唾液腺炎症病变发作之前检测到白细胞介素-1（IL-1）β和肿瘤坏死因子（TNF）的过表达，并且在MRL/lpr小鼠中也发现IL-6 mRNA的上调与自身免疫性涎腺炎一致。事实证明，诸如IL-1β、TNF和IL-6等炎性细胞因子作为诱导自身免疫现象的调节蛋白发挥着重要作用。此外，还分析了唾液腺组织中T细胞抗原受体β（TCR）β转录本的表达。从疾病发作开始，在浸润涎腺炎的T细胞中主要检测到Vβ8转录本，这表明携带TCR Vβ8的CD4 + T细胞在识别MRL/lpr小鼠自身免疫性涎腺炎中未知自身肽方面起着至关重要的作用。此外，干燥综合征样自身免疫病变成功转移到严重联合免疫缺陷（SCID）小鼠中，并且通过给予抗CD4和抗Vβ8单克隆抗体可以预防这些病变。本文将综述最近对MRL/lpr小鼠中发生的自身免疫性涎腺炎这些发病机制分析的观察结果。
