The present proposal is a continuation of our research into the pathogenesis and manipulation of adjuvant arthritis in Lewis rats using long-term lines and clones of T lymphocytes. One clone, A2b, could induce arthritis but not vaccinate against it. A second clone, A2c, in contrast, was not arthritogenic, but was only capable of inducing resistance to arthritis after a single intravenous inoculation of A2c. A2c could induce rapid and long-lasting remission in rats suffering from ongoing adjuvant arthritis. Thus, clone A2b served as a vehicle for investigating pathogenesis of arthritis and clone A2c served as an agent for studying manipulation of disease. A2b was found to respond to cartilage proteoglycan in addition to MT, indicating that adjuvant arthritis may arise through cross-reactivity between a bacterial epitope and a component of joint cartilage. We have also identified several monoclonal anti-mycobacterial antibodies that recognize cartilage proteoglycan.
The specific aims of the present proposal are to use arthritogenic clones and the monoclonal antibodies to define the antigenic relationship between MT and cartilage responsible for arthritis, and to use protective clones to elucidate the mechanism of induced resistance to arthritis as follows: a. Characterization of antigens of cartilage proteoglycans and mycobacteria recognized by arthritogenic or protective T lymphocyte clones and by cross-reactive monoclonal antibodies. b. Investigation of vaccination and therapy mediated by T lymphocyte clones: optimization of induction and analysis of mechanism. c. Development of clonotypic antibodies defining idiotypes of arthritogenic and protective clones. Use of anti-idiotypic antibodies to study and manipulate adjuvant arthritis.
| Cohen, I R (1992) Autoimmunity to hsp65 and the immunologic paradigm. Adv Intern Med 37:295-311 |
| Mor, F; Lohse, A W; Karin, N et al. (1990) Clinical modeling of T cell vaccination against autoimmune diseases in rats. Selection of antigen-specific T cells using a mitogen. J Clin Invest 85:1594-8 |
