Collagen type II (CII)-specific antibodies induce arthritis in the absence of T or B cells but the arthritis progression is enhanced by CII-reactive T cells
Collagen type II (CII)-specific antibodies induce arthritis in the absence of T or B cells but the arthritis progression is enhanced by CII-reactive T cells
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DOI：
10.1186/ar1217
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发表时间：
2004-01-01
影响因子：
4.9
通讯作者：
Holmdahl, R
中科院分区：
文献类型：
--
作者：
Nandakumar, KS;Bäcklund, J;Holmdahl, R
针对II型胶原蛋白的抗体（抗CII）是致关节炎的，并且在胶原蛋白诱导的关节炎的起始中具有关键作用。在这里，我们已经确定了T和B细胞在胶原抗体诱导的关节炎（CAIA）在关节炎的不同阶段的依赖性。缺乏B和/或T细胞的小鼠对CAIA敏感，表明即使在缺乏适应性免疫系统的情况下，抗体也会诱导关节炎。为了确定CII反应性T细胞是否在关节炎发病机制的效应器水平上在增强关节炎发展中起作用，我们建立了与CII反应的T细胞系。该T细胞系是寡克隆的，并对与A（q）II类分子结合的260-270位的主要CII表位的不同翻译后形式产生应答。重要的是，它与小鼠肽交叉反应，尽管它与A（q）分子的结合亲和力低于相应的大鼠肽。T细胞系本身不能在A（q）表达小鼠中诱导临床关节炎，即使这些小鼠在软骨中表达主要的异源CII表位，如在转基因MMC（突变的小鼠胶原）小鼠中。然而，抗CII单克隆抗体和CII反应性T细胞的联合治疗增强了严重关节炎的进展。
Antibodies against type II collagen (anti-CII) are arthritogenic and have a crucial role in the initiation of collagen-induced arthritis. Here, we have determined the dependence of T and B cells in collagen-antibody-induced arthritis (CAIA) during different phases of arthritis. Mice deficient for B and/or T cells were susceptible to the CAIA, showing that the antibodies induce arthritis even in the absence of an adaptive immune system. To determine whether CII-reactive T cells could have a role in enhancing arthritis development at the effector level of arthritis pathogenesis, we established a T cell line reactive with CII. This T cell line was oligoclonal and responded to different post-translational forms of the major CII epitope at position 260-270 bound to the A(q) class II molecule. Importantly, it cross-reacted with the mouse peptide although it is bound with lower affinity to the A(q) molecule than the corresponding rat peptide. The T cell line could not induce clinical arthritis per se in A(q)-expressing mice even if these mice expressed the major heterologous CII epitope in cartilage, as in the transgenic MMC (mutated mouse collagen) mouse. However, a combined treatment with anti-CII monoclonal antibodies and CII-reactive T cells enhanced the progression of severe arthritis.