Aberrant expression of class II MHC antigens by skeletal muscle endothelial cells in experimental autoimmune myositis.

Abstract

We recently described the induction of an inflammatory myopathy in SJL/J mice after injection of skeletal muscle Ag and adjuvant that is characterized by necrosis of muscle fibers associated with infiltrating mononuclear cells. In the present study, an immunohistologic analysis was performed to examine the phenotype of these infiltrating cells and to determine changes in cell-surface Ag expression in involved muscle. The predominant cells infiltrating muscle after induction of experimental autoimmune myositis (EAM) were found to be Mac-1+/I-A+ macrophages, representing 80 to 90% of all infiltrating cells, and CD4+ T lymphocytes, representing 10 to 15% of all infiltrating cells. Few CD8+ T cells, and no B cells, were seen in the involved muscles. Interestingly, endothelial cells in involved muscles were also noted to express class II MHC Ag. Aberrant I-A Ag expression was not observed on endothelial cells in other tissues examined, including kidney, liver, cardiac muscle, and lung. I-A Ag expression appeared to correlate with susceptibility to disease in that muscle endothelial cells remained negative after attempts to induce EAM in a nonsusceptible strain. Together, the data suggest that aberrant organ-specific class II MHC Ag expression and a response by CD4+ T cells may be pathogenetically involved in the muscle injury of EAM. In addition, the predominance of infiltrating macrophages suggests that these recruited cells may also be important in the immune-mediated muscle damage.