Löhr H F, Schlaak J F, Kollmannsperger S, Dienes H P, Meyer zum Büschenfelde K H, Gerken G
1. Department of Internal Medicine, Johannes-Gutenberg-University, Mainz, Germany.
Liver. 1996 Jun;16(3):174-82. doi: 10.1111/j.1600-0676.1996.tb00724.x.
The aim was to assess the specificity and functional significance of liver-infiltrating and peripheral blood T cells in chronic hepatitis C. Peripheral blood mononuclear cells hepatitis C virus from 50 of 58 (86.2%) patients with chronic hepatitis C virus infection and 6 of 28 (21.4%) controls showed a proliferative T cell response to at least one of 16 synthetic peptides covering highly conserved regions of the core, envelope (El) and non-structural regions (NS4) of hepatitis C virus. However, six immunodominant peptides were exclusively recognized by the proliferating blood mononuclear cells from 46 patients with chronic hepatitis C virus infection (79.3%). Fine specificity and HLA-restriction were studied with 15 peptide-specific CD4+ T cell lines and 23 T cell clones isolated from liver tissue and peripheral blood of 12 patients with chronic hepatitis C. It was demonstrated that the peptide-specific response of CD4+ T cells was restricted to the presence of autologous accessory cells and HLA-DR and -DP molecules. Eight peptide-specific T cell lines and five T cell clones derived from liver tissue and peripheral blood, released interferon-gamma (200-6600 pg/ml) and tumor necrosis factor-alpha (100-400 pg/ml) and no or little interleukin-4 (< 140 pg/ml) after peptide-specific or mitogeneic stimulation, thus resembling a Th1-like cytokine profile. Patients with active liver disease showed significantly higher proliferative responses to hepatitis C virus core peptides than asymptomatic hepatitis C virus carriers or complete responders to interferon therapy. In conclusion, class II-restricted CD4+ T cell responses to some immunodominant epitopes within the hepatitis core region correlated with disease activity in chronic hepatitis C virus infection. Functionally, liver-infiltrating and peripheral blood T cells released Th1-like cytokines in response to the specific stimulus. Thus, it can be suggested that CD4+ T cells can mediate the pathogenesis of chronic hepatitis C virus induced liver disease.
目的是评估慢性丙型肝炎中肝脏浸润性和外周血T细胞的特异性及功能意义。58例慢性丙型肝炎病毒感染患者中的50例（86.2%）以及28例对照中的6例（21.4%）的外周血单个核细胞对覆盖丙型肝炎病毒核心、包膜（E1）和非结构区（NS4）高度保守区域的16种合成肽中的至少一种表现出增殖性T细胞反应。然而，46例慢性丙型肝炎病毒感染患者（79.3%）的增殖性血单个核细胞仅识别六种免疫显性肽。对从12例慢性丙型肝炎患者的肝组织和外周血中分离出的15个肽特异性CD4⁺T细胞系和23个T细胞克隆进行了精细特异性和HLA限制性研究。结果表明，CD4⁺T细胞的肽特异性反应限于自体辅助细胞以及HLA-DR和-DP分子的存在。源自肝组织和外周血的8个肽特异性T细胞系和5个T细胞克隆在肽特异性或丝裂原刺激后释放干扰素-γ（200 - 6600 pg/ml）和肿瘤坏死因子-α（100 - 400 pg/ml），而白细胞介素-4释放极少或不释放（< 140 pg/ml），因此类似于Th1样细胞因子谱。活动性肝病患者对丙型肝炎病毒核心肽的增殖反应显著高于无症状丙型肝炎病毒携带者或干扰素治疗的完全应答者。总之，慢性丙型肝炎病毒感染中，II类限制性CD4⁺T细胞对肝炎核心区内某些免疫显性表位的反应与疾病活动相关。在功能上，肝脏浸润性和外周血T细胞对特异性刺激释放Th1样细胞因子。因此，可以认为CD4⁺T细胞可介导慢性丙型肝炎病毒诱导的肝病的发病机制。
