Kurokohchi Kazutaka, Arima Keiji, Masaki Tsutomu, Deguchi Akiihiro, Nakai Seiji, Morishita Asahiro, Yoneyama Hirohito, Ohgi Tomohiro, Ono Masahiro, Yoshitake Akira, Maeta Tsuyoshi, Mori Yoshihiro, Kohi Fumikazu, Nishioka Mikio, Kuriyama Shigeki
Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kagawa, Japan.
J Clin Immunol. 2006 Jul;26(4):323-30. doi: 10.1007/s10875-006-9030-6. Epub 2006 Jun 16.
Because the underlying mechanism of hepatocellular damages in autoimmune hepatitis (AIH) still remains unclear, analysis of CD28 and bcl-2 molecules, which are critical for T cell activation and survival, was performed in patients with AIH. The number of CD28(+)CD4(+) peripheral blood mononuclear cells (PBMC) in corticosteroid (CS)-treated patients was comparable to normal control individuals but decreased in untreated AIH patients. In contrast, the number of CD28(+)CD8(+) PBMC was decreased in both CS-treated and untreated AIH patients. Analysis of liver-infiltrating mononuclear cells (LIMC) showed that the number of CD28(+)CD4(+) and CD28(-)CD8(+) LIMC were positively correlated with the histology activity index score. Bcl-2(+)CD4(+) LIMC were observed in the portal area of the liver and the numbers fluctuated with disease activity during the time course after CS administration. By contrast, CD8(+) LIMC were shown not to express bcl-2. Taken collectively, these results suggest that bcl-2(+)CD28(+)CD4(+) and bcl-2(-)CD28(-)CD8(+) cells may play critical and distinct roles in hepatocellular damage in AIH.
由于自身免疫性肝炎（AIH）中肝细胞损伤的潜在机制仍不清楚，因此对AIH患者进行了对T细胞活化和存活至关重要的CD28和bcl-2分子分析。接受皮质类固醇（CS）治疗的患者外周血单核细胞（PBMC）中CD28(+)CD4(+)细胞数量与正常对照个体相当，但未治疗的AIH患者中该细胞数量减少。相比之下，接受CS治疗和未治疗的AIH患者中CD28(+)CD8(+) PBMC数量均减少。对肝浸润单核细胞（LIMC）的分析表明，CD28(+)CD4(+)和CD28(-)CD8(+) LIMC数量与组织学活动指数评分呈正相关。在肝脏门静脉区域观察到bcl-2(+)CD4(+) LIMC，且其数量在CS给药后的病程中随疾病活动而波动。相比之下，CD8(+) LIMC未显示表达bcl-2。总体而言，这些结果表明bcl-2(+)CD28(+)CD4(+)和bcl-2(-)CD28(-)CD8(+)细胞可能在AIH肝细胞损伤中发挥关键且不同的作用。
