Definitive Engagement of Cytotoxic CD8 T Cells in C Protein-Induced Myositis, a Murine Model of Polymyositis

作者：Sugihara Takahiko; Okiyama Naoko; Suzuki Mihoko; Kohyama Kuniko; Matsumoto Yoh; Miyasaka Nobuyuki; Kohsaka Hitoshi^*

来源：Arthritis and Rheumatism, 2010, 62(10): 3088-3092.

DOI：10.1002/art.27625

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.

• 出版日期2010-10