Kurokohchi Kazutaka, Masaki Tsutomu, Himoto Takashi, Deguchi Akihiro, Nakai Seiji, Morishita Asahiro, Yoneyama Hirohito, Kimura Yasuhiko, Watanabe Seishiro, Kuriyama Shigeki
Third Department of Internal Medicine, Kagawa University School of Medicine, Miki-cho, Kita-gun, Japan.
World J Gastroenterol. 2006 Apr 28;12(16):2523-9. doi: 10.3748/wjg.v12.i16.2523.
Although the pathogenic mechanism underlying autoimmune hepatitis (AIH) remains unclear, the immune system is thought to be critical for the progression of the disease. Cellular immune responses may be linked to the hepatocellular damage in AIH. Recently, much attention has been focused on the critical functions of costimulatory molecules expressed on mononuclear cells in the generation of effective T cell-mediated immune responses. Analysis of costimulatory molecule expressed on mononuclear cells from the patients with AIH may give us insight into the pathogenic mechanism of hepatocellular damage in AIH.
Peripheral blood mononuclear cells (PBMC) were taken from the patients with AIH (34 cases) and healthy controls (25 cases). Liver infiltrating mononuclear cells (LIMCs) were taken from the patients with AIH (18 cases), the patient with chronic hepatitis C (CH-C) (13 cases) and the patients with fatty liver (2 cases). Using flow cytometry, the cells were analyzed for the expression of costimulatory molecules, such as CD80, CD86, and CD152 (CTLA-4). The results were compared with clinical data such as the level of gammaglobulin, histological grade, presence or absence of corticosteroids administration and the response to corticosteroids.
The levels of CD80+, CD86+ and CD152+ PBMC were significantly reduced in the patients with AIH as compared with healthy controls. By contrast, those cells were significantly higher in LIMC than in PBMC of the patients with AIH. Especially, the level of CD86+ LIMC showed a marked increase irrespective of the degree of disease activity in the patients with AIH, although CD86+ cells were rarely present in PBMC. The levels of CD86+ cells were present in significantly higher frequency in patients with AIH than in the patients with CH-C. Furthermore, the patients with AIH with high levels of CD86+ LIMC showed good responses to corticosteroids, whereas 2 cases of AIH with low levels of CD86+ LIMC did not respond well.
These results suggest that LIMC over-expressing costimulatory molecules such as CD80 and CD86 appears to play a role in the pathogenesis of AIH. Especially, CD86 molecule expressed on the LIMC may be useful for the diagnosis of AIH and for the prediction of the therapeutic effects of corticosteroids on AIH.
尽管自身免疫性肝炎（AIH）的致病机制尚不清楚，但免疫系统被认为在该疾病的进展中起关键作用。细胞免疫反应可能与AIH中的肝细胞损伤有关。最近，人们将大量注意力集中在单核细胞上表达的共刺激分子在有效T细胞介导的免疫反应产生中的关键作用。分析AIH患者单核细胞上表达的共刺激分子可能有助于我们深入了解AIH中肝细胞损伤的致病机制。
从AIH患者（34例）和健康对照者（25例）中采集外周血单核细胞（PBMC）。从AIH患者（18例）、慢性丙型肝炎（CH-C）患者（13例）和脂肪肝患者（2例）中采集肝脏浸润单核细胞（LIMC）。使用流式细胞术分析细胞中共刺激分子如CD80、CD86和CD152（CTLA-4）的表达。将结果与临床数据如γ球蛋白水平、组织学分级、是否使用皮质类固醇以及对皮质类固醇的反应进行比较。
与健康对照相比，AIH患者中CD80 +、CD86 +和CD152 + PBMC的水平显著降低。相比之下，AIH患者的LIMC中这些细胞的水平明显高于PBMC。特别是，无论AIH患者的疾病活动程度如何，CD86 + LIMC的水平均显著升高，尽管PBMC中很少有CD86 +细胞。AIH患者中CD86 +细胞的频率明显高于CH-C患者。此外，CD86 + LIMC水平高的AIH患者对皮质类固醇反应良好，而2例CD86 + LIMC水平低的AIH患者反应不佳。
这些结果表明，LIMC过度表达共刺激分子如CD80和CD86似乎在AIH的发病机制中起作用。特别是，LIMC上表达的CD86分子可能有助于AIH的诊断以及预测皮质类固醇对AIH的治疗效果。
