Date of Award


Degree Type


Degree Name

Master of Science


Microbiology and Immunology


Dr. Ewa Cairns

Second Advisor

Dr. David A. Bell

Third Advisor

Dr. Mansour Haeryfar


MHC Class II molecules (e.g. DR4) expressing the Rheumatoid Arthritis (RA) shared epitope are strongly linked to the development of anti-citrulline (Cit) immune responses and the pathogenesis of RA. We have established a Cit-induced arthritis model (DR4 tg mice) where injection of citrullinated human fibrinogen (CithFib) induces anti- Cit immune responses and arthritis. The main objective of this study was to assess the role of T cells in this Cit- induced arthritis mouse model using CTLA4-Ig, an agent that blocks T cell activation. To accomplish this, DR4 tg mice were immunized with CithFib to induce arthritis. At the disease onset or peak, DR4 tg mice were treated with CTLA4-Ig or control human IgGl (hlgGl) or left untreated. Arthritis progression was monitored for 30 days, and then anti- Cit immune responses and the arthritogenicity of splenic lymphocytes from these mice were examined. The latter were done using adoptive lymphocyte transfers from CTLA4- Ig-treated mice or controls via intraperitoneal injection into naïve DR4 tg mice. The recipient mice also received intraarticular injection of CithFib or vehicle. The results demonstrated that CTLA4-Ig but not hlgGl treatment of arthritic DR4 tg mice significantly reduced ankle swelling and pathological joint damage in these mice. CTLA4-Ig, but not hlgGl treatment suppressed T cell proliferative responses to Cit. Unlike splenic lymphocytes from untreated arthritic mice, lymphocytes transferred from CTLA4-Ig-treated arthritic mice did not cause arthritis in recipient mice. The conclusion from this study is that Cit-specific T cells play a direct role in the development and progression of arthritis in this Cit-induced model for human RA.



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