Definitive Engagement of Cytotoxic CD8 T Cells in C Protein-Induced Myositis, a Murine Model of Polymyositis
Definitive Engagement of Cytotoxic CD8 T Cells in C Protein-Induced Myositis, a Murine Model of Polymyositis
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DOI：
10.1002/art.27625
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发表时间：
2010-10-01
影响因子：
--
通讯作者：
Kohsaka, Hitoshi
中科院分区：
文献类型：
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作者：
Sugihara, Takahiko;Okiyama, Naoko;Kohsaka, Hitoshi
Objective.为了证实细胞毒性CD 8 T细胞在小鼠多发性肌炎模型C蛋白诱导的肌炎（CIM）的发展中的致病作用。用骨骼肌C蛋白片段免疫β（2）-微球蛋白无效突变体、穿孔素无效突变体和野生型（WT）C57 BL/6小鼠以激发CIM。将用C蛋白脉冲的树突状细胞刺激的区域淋巴结CD 8或CD 4 T细胞过继转移至幼稚小鼠。组织学评价肌肉组织的炎症和损伤。与WT小鼠相比，β 2-微球蛋白缺失和穿孔素缺失突变小鼠的肌炎发生率显著降低。突变小鼠的炎症不那么严重，肌肉损伤的发生率也显著降低。来自CIM小鼠的淋巴结T细胞的连续转移在幼稚受体小鼠中诱导肌炎。CD 8 T细胞诱导的肌肉损伤明显重于CD 4 T细胞诱导的肌肉损伤。穿孔素介导的CD 8 T细胞的细胞毒性是CIM中肌肉损伤的决定性原因。
Objective. To substantiate a pathogenic role of cytotoxic CD8 T cells in the development of a murine polymyositis model, C protein-induced myositis (CIM).Methods. Beta(2)-microglobulin-null mutant, perforin-null mutant, and wild-type (WT) C57BL/6 mice were immunized with skeletal muscle C protein fragments to provoke CIM. Regional lymph node CD8 or CD4 T cells stimulated with C protein-pulsed dendritic cells were transferred adoptively to naive mice. Inflammation and damage of the muscle tissues were evaluated histologically.Results. The incidence of myositis development was significantly lower in beta(2)-microglobulin-null and perforin-null mutant mice compared with WT mice. Inflammation was less severe in mutant mice, and the incidence of muscle injury was reduced significantly. Adoptive transfer of lymph node T cells from mice with CIM induced myositis in naive recipient mice. The CD8 T cell-induced muscle injuries were significantly more severe than the CD4 T cell-induced muscle injuries.Conclusion. Perforin-mediated cytotoxicity by CD8 T cells is definitively responsible for muscle injury in CIM.