Cellular immune mechanisms in inflammatory myopathies.
The inflammatory myopathies include dermatomyositis, polymyositis, and inclusion body myositis. In dermatomyositis, muscle fiber injury is secondary to an antibody- or immune-complex-mediated immune response against a vascular-endothelial component. In polymyositis and inclusion body myositis, CD8+ T cells and macrophages invade and eventually destroy initially nonnecrotic muscle fibers. The autoaggressive T cells have the phenotype of activated (HLA-DR+) memory (CD45RO+) cells. T-cell receptor analyses indicate that the autoaggressive T cells are oligoclonal. In inflammatory lesions, muscle fibers express various cytoplasmic and surface molecules that are not detectable in normal fibers. These molecules, which include HLA class I antigens, heat-shock proteins, adhesion molecules, and Fas, are probably induced by locally secreted cytokines. The autoaggressive CD8+ T cells harbor granules containing perforin that aggregate near the contact zone with the target muscle fiber. This is consistent with a perforin- and secretion-dependent mechanism of muscle fiber injury. Many invaded muscle fibers also express the Fas "death receptor," but signs of apoptosis are absent.
Hohlfeld
R
R
Department of Neurology, Klinikum Grosshadern, University of Munich, Germany.
Engel
A G
AG
Goebels
N
N
Behrens
L
L
D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology; D009220:Myositis / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D015815:Cell Adhesion Molecules; D016207:Cytokines