Matsumoto I, Tsubota K, Satake Y, Kita Y, Matsumura R, Murata H, Namekawa T, Nishioka K, Iwamoto I, Saitoh Y, Sumida T
Second Department of Internal Medicine, School of Medicine, Chiba Univesity, Japan.
J Clin Invest. 1996 Apr 15;97(8):1969-77. doi: 10.1172/JCI118629.
Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lacrimal and salivary glands leading to symptomatic dry eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lacrimal glands and labial salivary glands are CD4 positive alphabeta T cells. To analyze the pathogenesis of T cells infiltrating into lacrimal and labial salivary glands, we examined T cell clonotype of these cells in both glands from four SS patients using PCR-single-strand conformation polymorphism (SSCP) and a sequencing method. SSCP analysis showed that some infiltrating T cells in both glands expand clonally, suggesting that the cells proliferate by antigen-driven stimulation. Intriguingly, six to sixteen identical T cell receptor (TCR) Vbeta genes were commonly found in lacrimal glands and labial salivary glands from individual patients. This indicates that some T cells infiltrating into both glands recognize the shared epitopes on autoantigens. Moreover, highly conserved amino acid sequence motifs were found in the TCR CDR3 region bearing the same TCR Vbeta family gene from four SS patients, supporting the notion that the shared epitopes on antigens are limited. In conclusion, these findings suggest that some autoreactive T cells infiltrating into the lips and eyes recognized restricted epitopes of a common autoantigen in patients with SS.
干燥综合征(SS)是一种自身免疫性疾病,其特征是淋巴细胞浸润泪腺和唾液腺,导致出现干眼症和口干症状。免疫组织学研究已阐明,泪腺和唇腺周围大多数浸润淋巴细胞为CD4阳性αβ T细胞。为分析浸润到泪腺和唇腺的T细胞的发病机制,我们采用聚合酶链反应-单链构象多态性(PCR-SSCP)和测序方法,检测了4例干燥综合征患者这两种腺体中这些细胞的T细胞克隆型。SSCP分析显示,两种腺体中的一些浸润T细胞呈克隆性扩增,提示这些细胞通过抗原驱动刺激而增殖。有趣的是,在个别患者的泪腺和唇腺中通常可发现6至16个相同的T细胞受体(TCR)Vβ基因。这表明,一些浸润到两种腺体的T细胞识别自身抗原上的共同表位。此外,在来自4例干燥综合征患者的携带相同TCR Vβ家族基因的TCR CDR3区域中发现了高度保守的氨基酸序列基序,支持抗原上的共同表位有限这一观点。总之,这些发现提示,浸润到嘴唇和眼睛的一些自身反应性T细胞识别干燥综合征患者中一种共同自身抗原的有限表位。