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 β₂-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.