C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells
C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells
复制标题
DOI：
10.1136/annrheumdis-2012-202055
复制
发表时间：
2013-07-01
影响因子：
27.4
通讯作者：
Holmdahl, Rikard
中科院分区：
文献类型：
--
作者：
Backlund, Johan;Li, Cuiqin;Holmdahl, Rikard
胶原诱导关节炎（CIA）传统上在MHC II类A(q)表达小鼠中进行，而大多数转基因小鼠具有C57BL/6背景（表达主要组织相容性复合体（MHC） II类区域的b单倍型）。然而，C57BL/6小鼠在鸡源性II型胶原蛋白（CII）免疫后发生关节炎，但关节炎易感性是可变的，免疫特异性尚未明确。目的建立C57BL/6背景下对CII具有更可预测和明确的免疫反应的CIA模型。结果C57BL/6小鼠在高剂量结核分枝杆菌佐剂的作用下，鸡和大鼠的CII均可致关节炎。然而，污染胃蛋白酶具有很强的免疫原性，对关节炎的发展至关重要。鸡或大鼠CII上的H-2(b)限制性T细胞表位无法确定，但C57BL/6背景上的A(q)表达可诱导T细胞对CII260-270表位产生反应，并延长关节炎的慢性程度。结论C57BL/6小鼠中推测的（自身）抗原及其致关节炎决定因素尚未公开，质疑该模型在解决T细胞驱动的关节炎病理途径中的价值。为了克服这一障碍，我们推荐MHC II类基因C57BL/6N。Q小鼠，表达A(Q)，与T细胞决定因子已被彻底表征。
Introduction Collagen-induced arthritis (CIA) has traditionally been performed in MHC class II A(q)-expressing mice, whereas most genetically modified mice are on the C57BL/6 background (expressing the b haplotype of the major histocompatibility complex (MHC) class II region). However, C57BL/6 mice develop arthritis after immunisation with chicken-derived collagen type II (CII), but arthritis susceptibility has been variable, and the immune specificity has not been clarified.Objective To establish a CIA model on the C57BL/6 background with a more predictable and defined immune response to CII.Results Both chicken and rat CII were arthritogenic in C57BL/6 mice provided they were introduced with high doses of Mycobacterium tuberculosis adjuvant. However, contaminating pepsin was strongly immunogenic and was essential for arthritis development. H-2(b)-restricted T cell epitopes on chicken or rat CII could not be identified, but expression of A(q) on the C57BL/6 background induced T cell response to the CII260-270 epitope, and also prolonged the arthritis to be more chronic.Conclusions The putative (auto) antigen and its arthritogenic determinants in C57BL/6 mice remains undisclosed, questioning the value of the model for addressing T cell-driven pathological pathways in arthritis. To circumvent this impediment, we recommend MHC class II congenic C57BL/6N.Q mice, expressing A(q), with which T cell determinants have been thoroughly characterised.