P088 Type I interferon protects against antigen induced arthritis independently of indolediamine 2, 3 dioxygenase

Abstract

Our earlier data have shown that type I interferon, when given at the time of antigen immunization can protect against mBSA induced arthritis (Type I IFN protects against arthritis, Eur J Immunol June 2011;41(6):1687–95). This protection ismanifested by inhibition of antigen specific proliferation of lymphocytes and decreased production of inflammatory cytokines, possibly resulting in immune tolerance. Indoleamine 2, 3 dioxygenase (IDO) is an important mediator of immune tolerance. Here we investigated if IFNa mediated arthritis protection and inhibition of antigen specific proliferation is dependent on IDO by inhibiting the enzymatic activity of IDO by 1 Methyl Tryptophan (1MT) at different time points during arthritis induction. Arthritis was induced by immunization with mBSA with or without 1000 U Interferon alpha (IFNα) at day 1 and 7 followed by intra-articular injection of mBSA at day 21. Inhibition of IDO activity, (10 mg 1-MT/30 g mice/day), either throughout the experiment from day −1 or from day 20, had no significant effect on IFNa mediated protection. Furthermore, in line with earlier data, the IFNa mediated arthritis protection in the IDO-inhibited group was also accompanied by lower antigen specific proliferation of lymph node cells and splenocytes restimulated with mBSA ex vivo at day 28. These results show that the tolerogenic mechanism underlying the IFNa mediated arthritis protection is independent of the enzymatic activity of IDO.