Definitive engagement of cytotoxic CD8 T cells in C protein–induced myositis, a murine model of polymyositis
✍ Scribed by Takahiko Sugihara; Naoko Okiyama; Mihoko Suzuki; Kuniko Kohyama; Yoh Matsumoto; Nobuyuki Miyasaka; Hitoshi Kohsaka
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 160 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
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 β~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.