Müntzing K, Lindberg C, Moslemi A-R, Oldfors A
Department of Pathology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Scand J Immunol. 2003 Aug;58(2):195-200. doi: 10.1046/j.1365-3083.2003.01251.x.
Inclusion body myositis (IBM) is a chronic inflammatory myopathy. The muscle histology is characterized by infiltration of T cells, which invade and apparently destroy muscle fibres. This study was performed to investigate whether predominant clones of muscle-infiltrating T cells are identical in different muscles and whether they persist over time in IBM. By reverse transcriptase-polymerase chain reaction, 25 T-cell receptor (TCR) variable beta (Vbeta) chain families and the complementarity-determining region 3 (CDR3) of the TCR were analysed in two different muscle biopsies of four patients with IBM. In two of the patients, the muscle biopsies were obtained from different muscles at one time point, whereas in two patients, the second biopsy was obtained 9 years after the first biopsy. T cells expressing predominant Vbeta families were analysed for clonality by fragment length analysis of the CDR3. Predominant Vbeta families were analysed by DNA sequencing to identify identical clones. Immunohistochemical staining of Vbeta families was performed to study the distribution of T cells expressing identified predominant Vbeta families. The muscle-infiltrating lymphocytes showed restricted expression of TCR Vbeta families. DNA sequencing proved that clonally expanded T cells were identical in different muscles and persisted 9 years after the first biopsy. Immunohistochemical analysis with Vbeta family-specific antibodies demonstrated the endomysial localization of these T cells in inflammatory cell infiltrates. Our results show that in IBM there is clonal restriction of TCR expression in muscle-infiltrating lymphocytes. Identical T-cell clones predominate in different muscles, and these clones persist for many years. These results indicate an important, continuous, antigen-driven inflammatory reaction in IBM.
包涵体肌炎（IBM）是一种慢性炎症性肌病。肌肉组织学特征为T细胞浸润，这些T细胞侵入并明显破坏肌纤维。本研究旨在调查不同肌肉中浸润肌肉的T细胞优势克隆是否相同，以及它们在IBM中是否随时间持续存在。通过逆转录聚合酶链反应，对4例IBM患者的两份不同肌肉活检标本中的25个T细胞受体（TCR）可变β（Vβ）链家族及TCR的互补决定区3（CDR3）进行了分析。其中2例患者在同一时间点从不同肌肉获取肌肉活检标本，而另外2例患者在首次活检9年后进行第二次活检。通过CDR3片段长度分析，对表达优势Vβ家族的T细胞进行克隆性分析。通过DNA测序分析优势Vβ家族，以鉴定相同克隆。对Vβ家族进行免疫组织化学染色，以研究表达已鉴定优势Vβ家族的T细胞的分布。浸润肌肉的淋巴细胞显示TCR Vβ家族表达受限。DNA测序证明，克隆性扩增的T细胞在不同肌肉中相同，且在首次活检9年后仍持续存在。用Vβ家族特异性抗体进行的免疫组织化学分析显示，这些T细胞在内膜肌层定位在炎性细胞浸润中。我们的结果表明，在IBM中，浸润肌肉的淋巴细胞中TCR表达存在克隆性限制。相同的T细胞克隆在不同肌肉中占主导地位，且这些克隆持续多年。这些结果表明IBM中存在重要的、持续的、抗原驱动的炎症反应。
