Immune Regulatory Function of Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase in Orally Tolerance to Type II Collagen-induced Animal Model

ABSTRACT

BACKGROUND: Immune regulatory dendritic cells (DCs) play an important role in maintaining self-tolerance. Recent evidences demonstrate that DCs expressing indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan catabolism, play an important role in immunoregulation and tolerance and induce T cell apoptosis. This study was devised to examine the role of IDO in the oral tolerance induction in collagen-induced arthritis (CIA) mouse model. METHODS: Beginning 2 weeks before immunization, CII was fed six times to DBA/1 mice and the effect on arthritis was assessed. In tolerized mice, CD11c+ DCs were isolated and stimulated with CII, IFN-gamma, and LPS with or without IDO inhibitor, 1-methyl-DL-tryptophan (1-MT) and IDO expression by CD11c+ DCs was analyzed using FACS and RT-PCR. The expression of IDO, MHC II, CD80, and CD86 by CD11c+ DCs were examined using confocal microscopy. Regulatory effect of CD11c+ DCs on Ag-specific T cell proliferative response to CII was examined by mixed lymphocyte reaction (MLR) with or without 1-MT. RESULTS: The proportion of IDO-expressing CD11c+ DCs was slightly higher in tolerized mice than in CIA mice and significantly increased after stimulation with CII, IFN-gamma, and LPS in an IDO- dependent manner. On confocal microscopic examination, the expression of IDO was higher and those of MHC II and CD86 were lower in CD11c+ DCs from tolerized mice compared to those from CIA mice. On MLR, CD11c+ DCs from tolerized mice inhibited T cell proliferative response to CII in an IDO-dependent manner. CONCLUSION: Enhanced IDO expression by CD11c+ DCs from tolerized mice may contribute to the regulation of proliferative response of CII-reactive T cells and could be involved in the induction of oral tolerance to CII.