Rats or mice immunized with type II collagen (CII) develop a polyarthritis with histologic, clinical, and radiographic manifestations resembling those found in patients with rheumatoid arthritis. This immunologically mediated model appears to be T cell dependent. To characterize the pathogenic and immunoregulatory mechanisms involved in the induction of collagen-induced arthritis (CIA) CII-specific T cell lines, clones, and T-T hybridomas have been developed in the rat system. Selected T cell lines and clones are pathogenic in adoptive transfer studies. T-T hybridomas, derived from these arthritogenic CII-specific T cells, recognize a cyanogen bromide (CB) cleavage fragment CB11 (representing approximately 25% of the CII molecule) which in mouse CIA has the capacity to induce or, in a separate protocol, prevent CIA. The proposed studies will define the arthritogenic epitopes on CB fragments in the rat and mouse systems. A set of overlapping peptides from arthritogenic CB fragments will be synthesized. These will be used to identify and characterized the specific amino acid sequence(s) of the epitope(s). In parallel studies, CB fragments and synthetic epitopes will be evaluated in rats and mice for their capacity to induce neonatal tolerance. This could also lead to the identification of putative arthritogenic epitopes. Additional experiments will attempt to identify specific peptide determinants that might suppress the induction of adult CIA. If suppression were demonstrated, these peptides would be evaluated for their ability to arrest or reverse ongoing CIA (a system comparable to therapeutic interventions in rheumatoid arthritis). These studies should expand our understanding of T cell mediated immunoregulatory processes in the induction and prevention of an experimental autoimmune model of chronic inflammatory synovitis.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Brahn, E; Lehman, T J; Peacock, D J et al. (1999) Suppression of coronary vasculitis in a murine model of Kawasaki disease using an angiogenesis inhibitor. Clin Immunol 90:147-51
Oliver, S J; Cheng, T P; Banquerigo, M L et al. (1998) The effect of thalidomide and 2 analogs on collagen induced arthritis. J Rheumatol 25:964-9
Hahn, B H (1997) The potential role of autologous stem cell transplantation in patients with systemic lupus erythematosus. J Rheumatol Suppl 48:89-93
Hahn, B H; Singh, R R; Tsao, B P et al. (1997) Peptides from Vh regions of antibodies to DNA activate T cell help to upregulate autoantibody synthesis. Lupus 6:330-2
Melo, M E; Goldschmidt, T J; Bhardwaj, V et al. (1996) Immune deviation during the induction of tolerance by way of nasal installation: nasal installation itself can induce Th-2 responses and exacerbation of disease. Ann N Y Acad Sci 778:408-11
Oliver, S J; Brahn, E (1996) Combination therapy in rheumatoid arthritis: the animal model perspective. J Rheumatol Suppl 44:56-60
Singh, R R; Hahn, B H; Sercarz, E E (1996) Neonatal peptide exposure can prime T cells and, upon subsequent immunization, induce their immune deviation: implications for antibody vs. T cell-mediated autoimmunity. J Exp Med 183:1613-21
Singh, R R; Ebling, F M; Sercarz, E E et al. (1995) Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus. J Clin Invest 96:2990-6
Zack, D J; Wong, A L; Stempniak, M et al. (1995) Two kappa immunoglobulin light chains are secreted by an anti-DNA hybridoma: implications for isotypic exclusion. Mol Immunol 32:1345-53
Zack, D J; Yamamoto, K; Wong, A L et al. (1995) DNA mimics a self-protein that may be a target for some anti-DNA antibodies in systemic lupus erythematosus. J Immunol 154:1987-94

Showing the most recent 10 out of 30 publications