Abstract

This project proposes to continue efforts to investigate the role of autoimmune responses to collagen in the pathogensis of connective tissue diseases. The rationale for this project is based on the increasing evidence that the articular manifestations of rheumatoid arthritis are, in part, attributable to T cell mediated processes. To elucidate more precisely the cellular immune mechanisms contributing to the induction of arthritis in rats or mice immunized with type II collagen, studies are planned to partially purify a lymphokine induced by type II collagen which is arthritogenic in rats and mice - arthritogenic factor. Other studies will attempt to analyze the T-cell repertoire to type II collagen in rats by cloning techniques. Additional experiments will further assess the possible involvement of hypersensitivity to type II collagen in the pathogenesis of adjuvant arthritis by ascertaining the cellular origin and biochemical and functional nature of the collagen induced arthritogenic factor activity present in this model. By identifying antigen-specific cellular effector mechanisms in animal models of inflammatory arthritis, these studies have the potential to elucidate pathways that may operate and be susceptible to modification in human disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
1R01AM037239-01
Application #
3154628
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1985-09-01
Project End
1986-04-30
Budget Start
1985-09-01
Budget End
1986-04-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code

  Publications

Kieval, R I; Young, C T; Prohazka, D et al. (1989) Evaluation of a modified hexose sugar, amiprilose hydrochloride, in experimental models of synovitis. J Rheumatol 16:67-74
Brahn, E; Trentham, D E (1989) Experimental synovitis induced by collagen-specific T cell lines. Cell Immunol 118:491-503
Trentham, D E (1988) Collagen arthritis in rats, arthritogenic lymphokines and other aspects. Int Rev Immunol 4:25-33
Helfgott, S M; Kieval, R I; Breedveld, F C et al. (1988) Detection of arthritogenic factor in adjuvant arthritis. J Immunol 140:1838-43
Caulfield, J P; Hein, A; Helfgott, S M et al. (1988) Intraarticular injection of arthritogenic factor causes mast cell degranulation, inflammation, fat necrosis, and synovial hyperplasia. Lab Invest 59:82-95
de Sousa, M; Dynesius-Trentham, R; Mota-Garcia, F et al. (1988) Activation of rat synovium by iron. Arthritis Rheum 31:653-61
De Sousa, M; Breedvelt, F; Dynesius-Trentham, R et al. (1988) Iron, iron-binding proteins and immune system cells. Ann N Y Acad Sci 526:310-22
Weinblatt, M E; Trentham, D E; Fraser, P A et al. (1988) Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum 31:167-75
Trentham, D E; Belli, J A; Bloomer, W D et al. (1987) 2,000-centiGray total lymphoid irradiation for refractory rheumatoid arthritis. Arthritis Rheum 30:980-7
Brahn, E; Trentham, D E (1987) Attenuation of collagen arthritis and modulation of delayed-type hypersensitivity by type II collagen reactive T-cell lines. Cell Immunol 109:139-47

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