Mizushima N, Kohsaka H, Tsubota K, Saito I, Miyasaka N
First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Clin Exp Immunol. 1995 Jul;101(1):33-8. doi: 10.1111/j.1365-2249.1995.tb02273.x.
Sjögren's syndrome (SS) is an autoimmune disease characterized by T cell infiltration into the salivary and lacrimal glands (LG). Previous studies on T cell receptor (TCR) usage in the minor salivary glands (SG) have yielded controversial results. We studied TCR beta gene usage of the T cells infiltrating to LG, which is the other major target organ of SS. Total RNA was extracted from fresh LG and SG biopsy samples, and peripheral blood mononuclear cells from five SS patients, and converted to cDNA. TCR V beta gene repertoire was then assessed with quantitative polymerase chain reaction (PCR) assay. Oligoclonality was studied by sequencing V-D-J junctional regions of the PCR products. The TCR V beta gene usage in LG was diverse in every patient irrespective of disease duration, and similar to that of peripheral lymphocytes from a corresponding patient. The junctional region sequences of over-expressed V beta families in LG T cells were heterogeneous. We did not find any identical clones shared by LG, SG and peripheral blood. These results showed that the infiltrating T cells in LG of SS patients are polyclonal, and LG and SG do not share the same dominant T cell clonotypes. These suggest that TCR-targeted disease manipulation may have a limited effect on SS.
干燥综合征(SS)是一种自身免疫性疾病,其特征为T细胞浸润至唾液腺和泪腺(LG)。先前关于小唾液腺(SG)中T细胞受体(TCR)使用情况的研究结果存在争议。我们研究了浸润至LG的T细胞的TCRβ基因使用情况,LG是SS的另一个主要靶器官。从5例SS患者的新鲜LG和SG活检样本以及外周血单个核细胞中提取总RNA,并将其转化为cDNA。然后用定量聚合酶链反应(PCR)分析评估TCR Vβ基因库。通过对PCR产物的V-D-J连接区进行测序来研究寡克隆性。无论病程长短,每位患者LG中的TCR Vβ基因使用情况都各不相同,且与相应患者外周淋巴细胞的情况相似。LG T细胞中过度表达的Vβ家族的连接区序列是异质的。我们未发现LG、SG和外周血共享任何相同的克隆。这些结果表明,SS患者LG中的浸润性T细胞是多克隆的,且LG和SG不共享相同的优势T细胞克隆型。这些提示针对TCR的疾病治疗对SS可能效果有限。