Katsumoto Y, Monden T, Takeda T, Haba A, Ito Y, Wakasugi E, Wakasugi T, Sekimoto M, Kobayashi T, Shiozaki H, Shimano T, Monden M
Department of Surgery II, Osaka University Medical School, Japan.
Br J Cancer. 1996 Jan;73(1):110-6. doi: 10.1038/bjc.1996.20.
We previously reported that the anti-tumour effect of OK-432 is considerably enhanced by its intratumoral injection together with fibrinogen. In the present study, we generated killer T cells by culturing tumour-infiltrating lymphocytes from thyroid cancer patients who had received this local immunotherapy. Phenotypic analysis revealed that the T cells were positive for CD3+, CD4+, Leu8-, CD45RO+ and T-cell receptor (TCR)alpha beta+, as well as showing strong surface expression of HLA-DR, CD25, LFA-1 and ICAM-1. The generated CD4+ T cells secreted interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, TNF-beta, and interleukin (IL)-6 (but not IL-4), and exhibited a high level of cytolytic activity against several tumour cell lines. The cytolytic activity of these T cells for Daudi cells was inhibited by preincubation with an anti-intercellular adhesion molecule (ICAM)-1 antibody, but not by preincubation with anti-TCR alpha beta, anti-CD2, or anti-LFA-1 antibodies. Pretreatment with anti-ICAM-1 antibody inhibited T-cell cytolytic activity, but not conjugation with target cells. In addition, incubation with immobilised anti-ICAM-1 enhanced the secretion of IFN-gamma by T cells. We conclude that ICAM-1 expressed on the effector cytotoxic CD4+ T lymphocytes delivers regulatory signals that enhance IFN-gamma secretion.
我们之前报道过，将OK-432与纤维蛋白原一起瘤内注射时，其抗肿瘤作用会显著增强。在本研究中，我们通过培养接受过这种局部免疫治疗的甲状腺癌患者的肿瘤浸润淋巴细胞来生成杀伤性T细胞。表型分析显示，这些T细胞CD3+、CD4+、Leu8-、CD45RO+和T细胞受体（TCR）αβ+呈阳性，同时HLA-DR、CD25、淋巴细胞功能相关抗原-1（LFA-1）和细胞间黏附分子-1（ICAM-1）有较强的表面表达。所生成的CD4+ T细胞分泌干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、TNF-β和白细胞介素（IL）-6（但不分泌IL-4），并且对几种肿瘤细胞系表现出高水平的细胞溶解活性。这些T细胞对Daudi细胞的细胞溶解活性可被抗ICAM-1抗体预孵育所抑制，但抗TCRαβ、抗CD2或抗LFA-1抗体预孵育则不能抑制。抗ICAM-1抗体预处理可抑制T细胞的细胞溶解活性，但不影响其与靶细胞的结合。此外，用固定化抗ICAM-1孵育可增强T细胞IFN-γ的分泌。我们得出结论，效应细胞毒性CD4+ T淋巴细胞上表达的ICAM-1传递调节信号，增强IFN-γ的分泌。
