Critical role of M-tuberculosis for dendritic cell maturation to induce collagen-induced arthritis in H-2b background of C57BL/6 mice
Critical role of M-tuberculosis for dendritic cell maturation to induce collagen-induced arthritis in H-2b background of C57BL/6 mice
复制标题
DOI：
10.1111/j.1365-2567.2006.02361.x
复制
发表时间：
2006-06-01
期刊：
影响因子：
6.4
通讯作者：
Shibuya, Akira
中科院分区：
文献类型：
--
作者：
Kai, Hirayasu;Shibuya, Kazuko;Shibuya, Akira
用含有高剂量而非低剂量结核分枝杆菌的完全弗氏佐剂（CFA）乳化的II型胶原（CII）免疫C57BL/6小鼠，即使在H-2(b)背景下，胶原诱导的关节炎（CIA）也可以诱导。本研究探讨了免疫方案诱导C57BL/6小鼠CIA的发病机制。我们采用定量逆转录聚合酶链反应检测了cia诱导的C57BL/6小鼠引流淋巴结（DLN）中细胞因子、共刺激分子和主要组织相容性复合体（MHC）ⅱ类的表达。我们还通过流式细胞术检测了结核分枝杆菌对这些分子在体外树突状细胞（DC）上表达的影响。最后，我们检测了用CII抗原免疫CFA中的结核分枝杆菌对CII诱导的C57BL/6小鼠DLN中特异性CD4（+）辅助T细胞启动的影响。干扰素- γ (ifn - γ)、白细胞介素-12p40 （IL-12p40）、共刺激分子CD40、CD80、CD86和MHC II类在cia诱导的C57BL/6小鼠DLN中的表达上调。这些共刺激分子的表达在体外高剂量而非低剂量结核分枝杆菌刺激后也上调。此外，要在DLN中启动CII抗原特异性的CD4（+）辅助性T细胞，需要使用含有高剂量（而不是低剂量）结核分枝杆菌的CFA对CII进行免疫。这些结果表明，在H-2(b)背景的C57BL/6小鼠DLN中，需要高剂量的结核分枝杆菌才能使DC成熟到足以启动针对CII抗原的CD4（+）辅助性T细胞。
Collagen-induced arthritis (CIA) can be induced even in CIA-resistant H-2(b) background of C57BL/6 mice when these mice are immunized with type II collagen (CII) emulsified in complete Freund's adjuvant (CFA) containing high, but not low, dose of Mycobacterium tuberculosis. Here, we investigated the pathogenesis of CIA in C57BL/6 mice induced by the immunizing protocol. We examined expressions of cytokines, costimulatory molecules and major histocompatibility complex (MHC) class II in draining lymph nodes (DLN) in CIA-induced C57BL/6 mice by quantitative reverse transcription-polymerase chain reaction. We also examined an effect of M. tuberculosis on the expression of these molecules on dendritic cells (DC) in vitro by flow cytometry. We finally examined an effect of M. tuberculosis in CFA used for immunization with CII antigen on priming of CD4(+) helper T cells specific to CII in DLN of CIA-induced C57BL/6 mice. The expression of interferon-gamma (IFN-gamma), Interleukin-12p40 (IL-12p40), costimulatory molecules CD40, CD80 and CD86 and MHC class II were up-regulated in DLN of CIA-induced C57BL/6 mice. Expressions of these costimulatory molecules were also up-regulated on DC after stimulation with high, but not low, dose of M. tuberculosis in vitro. Furthermore, priming of CD4(+) helper T cells specific to CII antigen in DLN required immunization with CII using CFA containing high, but not low, dose of M. tuberculosis. These results suggested that high dose of M. tuberculosis were required for maturation of DC enough to prime CD4(+) helper T cells specific to CII antigen in DLN of H-2(b) background of C57BL/6 mice.