Polymyositis is an acquired inflammatory myopathy of man. Several lines of evidence suggest that immune mechanisms may be involved in the pathogenesis of the muscle fiber injury and degeneration in human polymyositis. Although both cell-mediated and humoral immunity have been incriminated in this disorder, so far no clear cut mechanisms for the induction of disease has emerged from various studies. Experimental allergic myositis (EAM) is a useful animal model for human polymyositis. Detailed studies of the immune mechanisms responsible for EAM may lead to a better understanding of the role of the immune system in the pathogenesis of polymyositis. In this project, we propose to study the immune mechanisms in EAM. Specifically, we will 1) study the phenotype of the cells in the inflammatory muscle lesions at different stages in the evolution of the disease; 2) produce T-cell lines and clones reactive to muscle extract 3) try to transfer the disease with T-cell lines and clones reactive to muscle extract; and 4) try to identify the antigen(s) responsible for the induction of disease. To achieve these goals, we will: 1) determine the phenotype of the cells in EAM lesions with immunohistochemical techniques, using appropriate monoclonal antibodies to T-cell subsets, B-cells and macrophages; 2) produce muscle extract or muscle specific antigen reactive T-cell lines and clones using established methodologies; 3) try to transfer the disease to naive recipients with T-cell lines or clones; and 4) use a) western blot technique for identification of the muscle antigen(s) recognized by EAM serum; and b) a procedure involving separation of antigenic components by polyacrylamide gel electrophoresis followed transfer to nitrocellulose membrane and direct screening of blotted antigen(s) by T-cell proliferation assay. The target antigen(s) of humoral and cellular immunity identified by these methods will be isolated by preparative gel electrophoresis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AR039489-02
Application #
3457070
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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