Rheumatoid arthritis (RA) is characterized by chronic inflammation and proliferative activity in the synovial membrane of many joints. Though the initiating events are unknown, a prominent role for autoimmune processes in the perpetuation of the synovitis is indicated by the presence of rheumatoid factor and both cellular and humoral immunity to autologous antigens such as collagen. The murine model of type II collagen induced arthritis (CIA) shows many similarities to RA. The study will investigate the role of T-cell immunity in the response to type II collagen and subsequent development of inflammatory arthritis. The three main focal points of the study are 1) definition of the determinant or determinants expressed by type II collagen recognized by T-cells and which elicit the repsonse resulting in arthritis; 2) development of T-cell lines and clones reactive to type II collagen to be assessed for their arthritis-inducing potential; 3) in vivo manipulation of T-cell subsets and Ia expression by administration of monoclonal antibody and its effect on the immune response and CIA. Analysis of the immunologic and arthritogenic potential of peptides derived by cyanogen bromide digestion of type II collagen will allow definition of critical determinants associated with CIA. The production of T-cell lines and clones will be undertaken to provide a means for direct assessment of T-cell potential with regard to CIA induction. Administration of monoclonal antibody will complement the work with T-cell lines by permitting assessment of the in vivo role played by individual T-cell subsets in CIA induction and perpetuation. By defining the role of T-cells in CIA, further knowledge will be gained concerning the pathogenic and etiologic factors involved in RA, and new strategies for immunoregulatory therapies may be revealed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR036732-01
Application #
3157717
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-01-01
Project End
1988-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405