TY - JOUR
T1 - Mononuclear cells in myopathies
T2 - Quantitation of functionally distinct subsets, recognition of antigen-specific cell-mediated cytotoxicity in some diseases, and implications for the pathogenesis of the different inflammatory myopathies
AU - Engel, Andrew G.
AU - Arahata, Kiichi
N1 - Funding Information:
Until recently, the nature and significance of the predominantly mononuclear cellular infiltrates in muscle in inflammatory myopathies were not understood. According to current knowledge, such cells could represent macrophages with phagocytic, cytotoxic, or antigen-presenting properties; T cells with cytotoxic, suppressor, or helper capabilities; killer (K) and natural killer (NK) cells; and antibody-secreting B cells, l Cytotoxic T cells, like most other T cells, recognize antigens in association with major histocompatibility complex (MHC) gene products. 1,2 K cells attack antibody-coated target cells~; NK cells act without antibody, destroying foreign cells or cells with altered surface components. 4 muscular Research Laboratory, Mayo Clinic, Rochester, Minnesota, and the tDepartment of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Supported in part by NIH grant NS 6277 and a research center grant from the Muscular Dystrophy Association. Address correspondence and reprint requests to Dr. Engel: Mayo Clinic, Rochester, giN 55905.
PY - 1986/7
Y1 - 1986/7
N2 - Monoclonal antibodies reactive for B cells, T cells, T-cell subsets, killer (K) and natural killer (NK) cells, and the Ia antigen were used to analyzed mononuclear cell subsets in scleroderma (SD), dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), Duchenne dystrophy (DD), and normal muscle. The analysis, which was quantitative, was performed according to diagnosis and site of accumulation. Cells at perivascular, perimysial, and endomysial sites of accumulation, and cells focally surrounding and invading nonnecrotic muscle fibers, were analyzed separately. Individual antigens were localized in 2-μm serial sections, or multiple antigens were demonstrated in a given section by sequential paired immunofluorescence. The latter approach allowed the identification of the cell phenotypes in which functional properties are defined by multiple markers, e.g., T8+ and T4+ cells that are either activated or not activated, T8+ cells that are either cytotoxic or suppressor T cells, and K/NK cells of varying maturity and killing capability. The interactions of inflammatory cells of various types with each other and the muscle fiber were further investigated by immunoelectron microscopy. In SD, the findings provide evidence for a cell-mediated immune effector response against a connective tissue and/or vascular element. In DM, the effector response appears to be predominantly humoral. In PM and IBM (but not in DM or SD), there is invasion and destruction of nonnecrotic muscle fibers by cytotoxic T cells, with or without accompanying macrophages. Because T-cell-mediated injury is antigen-and major histocompatibility complex-restricted, clones of T cells must have been sensitized previously to a muscle fiber-associated surface antigen. The identity of the putative antigen (s) remains an important, unsolved question.
AB - Monoclonal antibodies reactive for B cells, T cells, T-cell subsets, killer (K) and natural killer (NK) cells, and the Ia antigen were used to analyzed mononuclear cell subsets in scleroderma (SD), dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), Duchenne dystrophy (DD), and normal muscle. The analysis, which was quantitative, was performed according to diagnosis and site of accumulation. Cells at perivascular, perimysial, and endomysial sites of accumulation, and cells focally surrounding and invading nonnecrotic muscle fibers, were analyzed separately. Individual antigens were localized in 2-μm serial sections, or multiple antigens were demonstrated in a given section by sequential paired immunofluorescence. The latter approach allowed the identification of the cell phenotypes in which functional properties are defined by multiple markers, e.g., T8+ and T4+ cells that are either activated or not activated, T8+ cells that are either cytotoxic or suppressor T cells, and K/NK cells of varying maturity and killing capability. The interactions of inflammatory cells of various types with each other and the muscle fiber were further investigated by immunoelectron microscopy. In SD, the findings provide evidence for a cell-mediated immune effector response against a connective tissue and/or vascular element. In DM, the effector response appears to be predominantly humoral. In PM and IBM (but not in DM or SD), there is invasion and destruction of nonnecrotic muscle fibers by cytotoxic T cells, with or without accompanying macrophages. Because T-cell-mediated injury is antigen-and major histocompatibility complex-restricted, clones of T cells must have been sensitized previously to a muscle fiber-associated surface antigen. The identity of the putative antigen (s) remains an important, unsolved question.
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U2 - 10.1016/S0046-8177(86)80180-0
DO - 10.1016/S0046-8177(86)80180-0
M3 - Article
C2 - 3459704
AN - SCOPUS:0022510445
SN - 0046-8177
VL - 17
SP - 704
EP - 721
JO - Human Pathology
JF - Human Pathology
IS - 7
ER -