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在干燥综合征的MRL/lpr小鼠模型自身免疫性涎腺炎发展的特定阶段中,T细胞受体Vβ基因使用存在偏差。

Biased T cell receptor V beta gene usage during specific stages of the development of autoimmune sialadenitis in the MRL/lpr mouse model of Sjögren's syndrome.

作者信息

Hayashi Y, Hamano H, Haneji N, Ishimaru N, Yanagi K

机构信息

Department of Pathology, Tokushima University School of Dentistry, Japan.

出版信息

Arthritis Rheum. 1995 Aug;38(8):1077-84. doi: 10.1002/art.1780380809.

DOI:10.1002/art.1780380809
PMID:7639803
Abstract

OBJECTIVE

To analyze the repertoire of T cell receptor (TCR) V beta gene transcribed and expressed within the autoimmune lesions of the salivary gland in the MRL/lpr mouse model of Sjögren's syndrome.

METHODS

Monoclonal antibodies (MAb) were used to determine the prevalence of selected V gene elements on T cell infiltrates from salivary glands of MRL/lpr mice. To analyze TCR V beta gene usage, we used reverse-transcriptase polymerase chain reaction (RT-PCR) and single-strand conformational polymorphism (SSCP) analyses.

RESULTS

A predominance of V beta 8+ T cells was detected within the inflammatory lesions during development of autoimmune disease (confirmed by flow cytometry). RT-PCR analysis revealed that in autoimmune sialadenitis, the predominant expression of the V beta 8 gene segment began in the early stages of disease (2-month-old mice) and increased over time. Extensive age-related diversity of TCR V beta gene usage was also observed. SSCP analysis demonstrated a distinct and common binding pattern of the V beta 8 gene PCR product from the cell infiltrates during the course of the disease.

CONCLUSION

Our data suggest that in the MRL/lpr mouse model of Sjögren's syndrome, there is restricted usage of TCR V beta elements according to the stage of the disease, and that V beta 8 are probably used preferentially in the recognition of a single unknown self antigen in the salivary gland.

摘要

目的

分析干燥综合征MRL/lpr小鼠模型唾液腺自身免疫性病变中转录并表达的T细胞受体(TCR)Vβ基因库。

方法

使用单克隆抗体(MAb)来确定MRL/lpr小鼠唾液腺T细胞浸润中选定V基因元件的流行情况。为了分析TCR Vβ基因的使用情况,我们采用了逆转录聚合酶链反应(RT-PCR)和单链构象多态性(SSCP)分析。

结果

在自身免疫性疾病发展过程中的炎性病变内检测到Vβ8+ T细胞占优势(通过流式细胞术证实)。RT-PCR分析显示,在自身免疫性涎腺炎中,Vβ8基因片段的主要表达始于疾病早期(2月龄小鼠),并随时间增加。还观察到TCR Vβ基因使用存在广泛的年龄相关多样性。SSCP分析表明,在疾病过程中,来自细胞浸润的Vβ8基因PCR产物具有独特且常见的结合模式。

结论

我们的数据表明,在干燥综合征的MRL/lpr小鼠模型中,根据疾病阶段,TCR Vβ元件的使用受到限制,并且Vβ8可能在识别唾液腺中单一未知自身抗原时被优先使用。

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