Yanagi K, Haneji N, Ishimaru N, Saito I, Hayashi Y
The Department of Pathology, Tokushima University School of Dentistry, Japan.
Clin Exp Immunol. 1997 Dec;110(3):440-6. doi: 10.1046/j.1365-2249.1997.4271445.x.
The NOD mouse develops spontaneous autoimmune sialadenitis besides a well characterized T cell-mediated autoimmune insulitis. We used reverse transcriptase-polymerase chain reaction (RT-PCR) to analyse the repertoire of T cell receptor (TCR) Vbeta chain genes expressed in the isolated infiltrating cells from affected salivary glands. Immunohistochemical analysis showed that the vast majority of inflammatory infiltrates in the salivary glands were CD4+ Vbeta8+ and CD4+ Vbeta6+ T cells, whereas CD8+ T cells and B220+ B cells were fewer in number. Predominant expression of the Vbeta8 and Vbeta6 gene segment was detected in the infiltrating cells in the salivary glands very early, and age-related diversity of TCR Vbeta gene usage was observed. Single-strand conformation polymorphism (SSCP) analysis demonstrated a strikingly symmetrical distribution of expanded clones in the PCR products of the Vbeta8 and Vbeta6 gene in the cells infiltrating the salivary glands. Nucleotide sequencing of amplified TCR Vbeta cDNA revealed that T cell clonotypes had a high incidence of identical clones, indicating that the immune response in NOD sialadenitis is driven by common stimuli. These findings suggest that in spontaneous autoimmune sialadenitis of NOD mice, there may be a restricted usage of TCR Vbeta elements in the early stage of the autoimmune lesion to recognize self-antigen in organ-specific autoimmune sialadenitis.
除了具有特征明确的T细胞介导的自身免疫性胰岛炎外,NOD小鼠还会发生自发性自身免疫性涎腺炎。我们使用逆转录聚合酶链反应(RT-PCR)分析从受影响的唾液腺分离出的浸润细胞中表达的T细胞受体(TCR)Vβ链基因库。免疫组织化学分析表明,唾液腺中绝大多数炎性浸润细胞是CD4 + Vβ8 +和CD4 + Vβ6 + T细胞,而CD8 + T细胞和B220 + B细胞数量较少。在唾液腺浸润细胞中很早就检测到Vβ8和Vβ6基因片段的主要表达,并观察到TCR Vβ基因使用的年龄相关多样性。单链构象多态性(SSCP)分析表明,在浸润唾液腺的细胞中,Vβ8和Vβ6基因的PCR产物中扩增克隆呈现出惊人的对称分布。对扩增的TCR Vβ cDNA进行核苷酸测序发现,T细胞克隆型中相同克隆的发生率很高,这表明NOD涎腺炎中的免疫反应是由共同刺激驱动的。这些发现表明,在NOD小鼠的自发性自身免疫性涎腺炎中,在自身免疫病变的早期阶段,TCR Vβ元件的使用可能受到限制,以识别器官特异性自身免疫性涎腺炎中的自身抗原。