Definitive engagement of cytotoxic CD8 T cells in C protein–induced myositis, a murine model of polymyositis

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.