CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis
CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis
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DOI：
10.1016/j.jaut.2008.05.003
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发表时间：
2008-09-01
影响因子：
12.8
通讯作者：
Akashi, Koichi
中科院分区：
文献类型：
--
作者：
Shimoda, Shinji;Miyakawa, Hiroshi;Akashi, Koichi
大约5%的原发性胆汁性肝硬变患者缺乏特征性的抗线粒体抗体(AMA)。然而，临床上AMA(+)和AMA(-)患者是相似的。使用AMA 4和AMA患者，我们使用有限稀释法和定量的干扰素-γ、IL-10和IL-4来定量对主要的CD4T细胞表位PDC-E2 163-176作出反应的自身反应性T细胞的频率。此外，基于PBC患者和健康受试者都有识别PDC-E163-176的CD_4(+)T细胞但具有不同的共刺激要求的数据，使用两种不同的抗原提呈细胞系统进行检测：自体外周血单个核细胞(PBMC)或HLADR53转基因小鼠成纤维细胞系(L-DR53)。当共刺激失活的L-DR53作为APC时，AMA和AMA患者的PDC-E2CD4T细胞频率和产生干扰素-γ的能力相同，但正常人的PDC-E2CD4T细胞频率和产生干扰素-γ的能力明显降低，IL-10的产生在三组中都是相似的。因此，在PBC中，对关键的自身抗原PDC-E2具有“普遍的”自身反应性的CD4IT细胞免疫反应。这些观察结果强调，PBC中的线粒体自身反应是一种多谱系反应，因此，AMA阴性的PBC可能是完全不合时宜的，只涉及血清自身抗体。(C)2008爱思唯尔有限公司。所有比赛预留。
Approximately 5% of patients with primary biliary cirrhosis (PBC) lack characteristic anti-mitochondrial antibodies (AMA). Yet clinically AMA(+) and AMA(-) patients are similar. Using both AMA 4 and AMA- patients, we quantitated the frequency of autoreactive T cells that respond to the major CD4 T-cell epitope, PDC-E2 163-176, using limiting dilution assays and quantitation of IFN-gamma, IL-10 and IL-4. Further, based on data that both PBC patients and healthy subjects have CD4(+) T cells that recognize PDC-E2 163-176 but with differing costimulation requirements, assays were performed using two different antigen-presenting cell (APC) systems: either autologous peripheral blood mononuclear cells (PBMC) or HLA DR53 transfected mouse fibroblast cell lines (L-DR53). When costimulation-incompetent L-DR53 were used as APCs, the PDC-E2 CD4 T-cell frequency and capacity for IFN-gamma production were equivalent in both AMA and AMA- patients but the frequencies of such cells were significantly lower in normals, with IL-10 production similar in all three groups. Thus, in PBC there is 'universal' autoreactive CD4 I T-cell immune responsiveness to the critical autoantigen, PDC-E2. These observations emphasize that the mitochondrial autoreactivity in PBC is a muiti-lineage response and hence, AMA-negative PBC may be ail anachronism that refers only to sera autoantibodies. (C) 2008 Elsevier Ltd. All Fights reserved.