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제2형 콜라겐 경구관용 유도 동물모델에서 수지상 세포의 Indoleamine 2,3-dioxygenase 의존성 관절염 항원 특이 T세포 증식반응 제어 연구

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

박성환|박경수|김호연|윤종현|민준기|조미라|조영규|민소연|박민정
대한면역학회 (The Korean Association of Immunologists)|2005.12|Immune Network|제5권 제4호|pp. 221-231

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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-γ, 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-γ, 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.

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