Adjuvant arthritis (AA) is inducible in Lewis rats by injection of heat-killed M. tuberculosis and it serves as an excellent model for human rheumatoid arthritis (RA). The 65 kD mycobacterial heat-shock protein (Bhsp65) is the focus of the T-cell responses of arthritic Lewis rats. T cells specific for the determinant (epitope) region 180-188/177-191 of Bhsp65 have been shown to be pathogenic in nature, whereas those primed by the Bhsp65 carboxy-terminal determinants (BCTD) are disease-regulating in nature. We hypothesize that the protective/beneficial effect of Celastrus orbiculatus (Celastrus) against arthritis (AA) involves differential modulation of the balance between T cell responses to the pathogenic and/or regulatory determinants of Bhsp65. This could be achieved by the action of Celastrus either on the function of the antigen presenting cells (APC) or on cytokine secretion (immune deviation from Thl to Th2, or TGF-beta secretion) by the Bhsp65-specific T cells, or both. We plan to test this proposition in our study. The results of this study would help in establishing a reliable scientific basis for use of Celastrus in autoimmune arthritis, and in developing better therapeutic approaches for patients with RA.
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