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Cellular immune mechanisms in inflammatory myopathies
R Hohlfeld1, A G Engel, N Goebels
1Department of Neurology, Klinikum Grosshadern, University of Munich, Germany.
Current Opinion in Rheumatology
|February 12, 1998
Summary
Inflammatory myopathies involve immune cells attacking muscle fibers. In polymyositis and inclusion body myositis, CD8+ T cells use perforin to damage muscle, while dermatomyositis involves immune complexes targeting blood vessels.
Area of Science:
- Immunology
- Neurology
- Pathology
Background:
- Inflammatory myopathies, including dermatomyositis, polymyositis, and inclusion body myositis, are debilitating autoimmune diseases affecting muscle.
- Muscle fiber injury mechanisms differ: dermatomyositis involves antibody/immune-complex attack on vasculature, while polymyositis and inclusion body myositis feature T-cell and macrophage invasion of muscle fibers.
Purpose of the Study:
- To elucidate the specific immune mechanisms and cellular players involved in muscle fiber injury in different inflammatory myopathies.
- To characterize the phenotype and cytotoxic mechanisms of autoaggressive T cells in polymyositis and inclusion body myositis.
Main Methods:
- Analysis of muscle biopsy samples from patients with inflammatory myopathies.
- Immunohistochemistry to identify immune cell infiltrates (CD8+ T cells, macrophages) and expressional changes in muscle fibers (HLA class I, heat-shock proteins, adhesion molecules, Fas).
- T-cell receptor analysis to assess the clonality of infiltrating T cells.
- Assessment of cytotoxic pathways, including perforin and Fas-mediated apoptosis.
Main Results:
- In polymyositis and inclusion body myositis, activated, memory CD8+ T cells and macrophages invade and destroy muscle fibers.
- Autoaggressive T cells in these conditions are oligoclonal and express HLA-DR and CD45RO.
- Muscle fibers in inflammatory lesions upregulate molecules like HLA class I, heat-shock proteins, adhesion molecules, and Fas, likely induced by cytokines.
- CD8+ T cells utilize perforin-dependent mechanisms for muscle fiber injury, with granules accumulating at the contact zone.
- While Fas is expressed on invaded fibers, classical apoptosis is not consistently observed.
Conclusions:
- Muscle fiber injury in polymyositis and inclusion body myositis is mediated by cytotoxic CD8+ T cells employing a perforin-dependent mechanism.
- The upregulation of various molecules on muscle fibers suggests a complex inflammatory environment contributing to pathogenesis.
- Distinct immunological pathways underlie dermatomyositis versus polymyositis/inclusion body myositis, highlighting the need for targeted therapies.