Usuda S, Yoshizawa K, Yabu K, Kiyosawa K
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
J Gastroenterol Hepatol. 1993 Nov-Dec;8(6):517-23. doi: 10.1111/j.1440-1746.1993.tb01645.x.
We performed a detailed analysis of immune responses in a hepatocellular carcinoma (HCC) cell line and effector cells obtained from a patient with HCC. We examined the cytotoxic activity of natural killer (NK) cells, lymphokine-activated killer (LAK) cells and cytotoxic T lymphocytes (CTL) against an autologous tumour cell line (SUHC-1) to investigate the immune mechanism of human lymphocytes against HCC cells. Cytotoxic T lymphocytes were induced by co-culturing of peripheral blood lymphocytes (PBL) and SUHC-1 cells, mixed lymphocyte and tumour cell culture (MLTC). The susceptibility of SUHC-1 to NK and LAK cells was similar to that of other allogeneic cell lines, such as K562, PLC/PRF/5 and Mahlavu. Effector cells induced in the primary MLTC had high cytotoxic activity but were not specific for SUHC-1. Cytotoxic T lymphocytes with specific activity against SUHC-1 were induced after PBL were stimulated five times at 7-10 day intervals with SUHC-1 and low-dose recombinant interleukin-2 (rIL-2), suggesting that as the culture progressed, broadly reactive effector cells disappeared and specific effector cells survived. The specific effector cells were identified as CD3+/CD4+ and CD3+/CD8+ T-lymphocyte subsets. The recognition mechanisms of CD3+/CD4+ CTL remain unresolved because the cytotoxicities were not inhibited by anti-CD4 and anti-major histocompatibility complex (MHC) class II monoclonal antibodies (MoAb). Treatment of cells with anti-CD3, anti-CD8 and anti-MHC class I MoAb partially inhibited lysis. These results demonstrated that the T-cell receptor (TCR)/CD3 complex appeared to be involved in SUHC-1 specific antigen recognition and antigen recognition of CD3+/CD8+ CTL was MHC class I restricted.
我们对一种肝癌(HCC)细胞系以及从一名肝癌患者获取的效应细胞中的免疫反应进行了详细分析。我们检测了自然杀伤(NK)细胞、淋巴因子激活的杀伤(LAK)细胞和细胞毒性T淋巴细胞(CTL)对自体肿瘤细胞系(SUHC-1)的细胞毒性活性,以研究人类淋巴细胞针对肝癌细胞的免疫机制。细胞毒性T淋巴细胞是通过外周血淋巴细胞(PBL)与SUHC-1细胞共培养、混合淋巴细胞和肿瘤细胞培养(MLTC)诱导产生的。SUHC-1对NK和LAK细胞的敏感性与其他异基因细胞系类似,如K562、PLC/PRF/5和Mahlavu。在初次MLTC中诱导产生的效应细胞具有高细胞毒性活性,但对SUHC-1不具有特异性。在用SUHC-1和低剂量重组白细胞介素-2(rIL-2)以7 - 10天的间隔刺激PBL五次后,诱导出了对SUHC-1具有特异性活性的细胞毒性T淋巴细胞,这表明随着培养的进行,广泛反应性的效应细胞消失,特异性效应细胞存活下来。特异性效应细胞被鉴定为CD3 + /CD4 + 和CD3 + /CD8 + T淋巴细胞亚群。CD3 + /CD4 + CTL的识别机制仍未明确,因为细胞毒性未被抗CD4和抗主要组织相容性复合体(MHC)II类单克隆抗体(MoAb)抑制。用抗CD3、抗CD8和抗MHC I类MoAb处理细胞可部分抑制裂解。这些结果表明,T细胞受体(TCR)/CD3复合体似乎参与了SUHC-1特异性抗原的识别,并且CD3 + /CD8 + CTL的抗原识别受MHC I类限制。