Cellular aspects of myositis

Polymyositis, dermatomyositis, and inclusion-body myositis are characterized by muscle cell infiltration and specific alterations on or within muscle fibers. Infiltrating immune cells (ie, T or B lymphocytes, macrophages, and natural killer cells) have distinctive distributions in these conditions: increased presence of CD8+/MHC I-restricted T lymphocytes at endomysial sites in polymyositis and more B than T lymphocytes perivascularly in muscles of dermatomyositis patients. Muscle-infiltrating T lymphocytes mainly express alpha beta T cell receptors (TCRs) in polymyositis; they also express TCRs characterized by oligoclonal V beta repertoire, with a consensus motif indicating a conventional antigen as target of the immune attack. In inclusion-body myositis, TCRs with oligoclonal V beta also are found, but no consensus motif has been identified, suggesting possible superantigen involvement in lymphocyte recruitment. Sequence analysis of TCRs in these lymphocytes has provided insight into the probable nature of the antigenic stimulus and into recruitment of these cells to the inflammation sites. T cell- or natural killer cell-mediated cytotoxic agents have been characterized by messenger RNA or protein expression in these inflammatory myopathies, and the roles of other cytokines in the inflammation processes have been determined. In vivo and in vitro studies on muscle cells have assessed their functions as target cells or antigen-presenting cells. Combined molecular and cellular immunology studies on effector and target cells are expected to clarify the pathogenetic mechanisms underlying these inflammatory myopathies in the near future.