Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis
Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis
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DOI：
10.1172/jci118749
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发表时间：
1996-06-15
影响因子：
15.9
通讯作者：
Hohlfeld, R
中科院分区：
文献类型：
--
作者：
Goebels, N;Michaelis, D;Hohlfeld, R
多发性肌炎（PM）和皮肌炎（DM）是骨骼肌的典型炎症性疾病。在PM中，CD8+ T细胞侵入并破坏肌纤维，而在DM中，体液效应机制占主导地位。我们通过半定量PCR、免疫组织化学和激光共聚焦显微镜研究了PM和DM肌肉中炎性细胞中细胞毒性介质穿孔素的表达。两种疾病均存在大量表达穿孔素的CD3+CD8+和CD3+ CD4+ T细胞，但穿孔素在细胞内的定位存在明显差异。糖尿病组穿孔素随机分布于炎性T细胞胞浆内。相比之下，43%的CD8+ T细胞，接触肌纤维在PM显示穿孔素位于矢量朝向目标肌纤维。结果表明：（a）在DM中观察到的肌肉浸润T细胞的细胞质中穿孔素的随机分布反映了非特异性激活，（B）仅在PM中观察到的矢量方向反映了通过T细胞受体对肌纤维表面抗原的特异性识别，指出了肌纤维损伤的穿孔素和分泌依赖性机制。
Polymyositis (PM) and dermatomyositis (DM) are the prototypical inflammatory diseases of skeletal muscle. In PM, CD8+ T cells invade and destroy muscle fibers, whereas humoral effector mechanisms prevail in DM, We studied the expression of the cytotoxic mediator perforin in inflammatory cells in PM and DM muscle by semiquantitative PCR, immunohistochemistry and confocal laser microscopy, Similar levels of perforin mRNA were expressed in PM and DM, and abundant perforin-expressing CD3+CD8+ and CD3+ CD4+ T cells were observed in both diseases, However, there was a striking difference in the intracellular localization of perforin. In DM, perforin was distributed randomly in the cytoplasm of the inflammatory T cells. In contrast, 43% of the CD8+ T cells that contacted a muscle fiber in PM showed perforin located vectorially towards the target muscle fiber. The results suggest (a) that the random distribution of perforin in the cytoplasm of muscle-infiltrating T cells observed in DM reflects nonspecific activation, and (b) that the vectorial orientation observed only in PM reflects the specific recognition via the T cell receptor of an antigen on the muscle fiber surface, pointing to a perforin- and secretion-dependent mechanism of muscle fiber injury.