Mononuclear cells in myopathies: 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

Andrew G Engel, Kiichi Arahata

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)704-721
Number of pages18
JournalHuman Pathology
Volume17
Issue number7
DOIs
StatePublished - 1986

Fingerprint

Myositis
Muscular Diseases
Dermatomyositis
T-Lymphocytes
Antigens
Muscles
Inclusion Body Myositis
CD8-Positive T-Lymphocytes
Natural Killer Cells
CD4-Positive T-Lymphocytes
Polymyositis
Immunoelectron Microscopy
Histocompatibility Antigens Class II
T-Lymphocyte Subsets
Surface Antigens
Major Histocompatibility Complex
Cell Communication
Connective Tissue
Fluorescent Antibody Technique
Blood Vessels

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{529d53166b4347aaabf02f4f284f3424,
title = "Mononuclear cells in myopathies: 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",
abstract = "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.",
author = "Engel, {Andrew G} and Kiichi Arahata",
year = "1986",
doi = "10.1016/S0046-8177(86)80180-0",
language = "English (US)",
volume = "17",
pages = "704--721",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "7",

}

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

PY - 1986

Y1 - 1986

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.

UR - http://www.scopus.com/inward/record.url?scp=0022510445&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022510445&partnerID=8YFLogxK

U2 - 10.1016/S0046-8177(86)80180-0

DO - 10.1016/S0046-8177(86)80180-0

M3 - Article

C2 - 3459704

AN - SCOPUS:0022510445

VL - 17

SP - 704

EP - 721

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 7

ER -