Polymyositis inpatients infected with human T‐cell leukemia virus type I: The role of the virus in the cause of the disease

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Abstract
To investigate the mechanism of polymyositis in human T-cell leukemia virus type 1 (HTLV-I) infection, we studied 6 HTLV-I–positive patients, 3 with polymyositis and 3 with adult T-cell leukemia but without clinical signs of muscle disease, by (a) quantitative single or double immunocytochemistry on serial 4-μm-thick muscle biopsy sections using antibodies to lymphocyte subsets, major histocompatibility complex (MHC) antigens, and HTLV-I proteins; (b) polymerase chain reaction using HTLV-I primers in the RNA and DNA extrcted from 50 μg of muscle tissue or from serial 5-μm-thick fresh-frozen tissue sections; and (c) cocultures of the patients' HTLV-I–positive peripher blood lymphocytes with their homologous muscles searching for replication of HTLV-I within the myotubes. In the muscle of patients with HTLV-I–associated myopathy, the predominant endomysial cells surrounding healthy muscle fibers were CD8+ cells followed by CD4+ cells and macrophages. MHC-I antigens were ubiquitous in the muscles of all 6 patients, even in those without endomysial inflammation. HTLV-I sequences were amplified from the whole muscle biopsy specimens but the cells harboring viral antigens were rare endomysial macrophages and not muscle fibers. Although HTLV-I sequences were amplified from all the patients' peripheral blood lymphocytes, these cells did not exert myotoxicity or resulted in viral replication in cocultures with their homologous myotubes. We conclude that in HTLV-I polymyositis (a) the HTLV-I sequences amplified from the whole muscle biopsy specimens are related to scattered HTLV-I–positive endomysial macrophages; (b) HTLV-I and HTLV-I–positive lymphocytes do not infect the muscle in vivo or in vitro; and (c) the virus, which perists in tissues other than muscle, triggers the activationof autoaggressive T cells that cause a T-cell–mediated and MHC-I–restricted myocytotoxicity.