β-环糊精-苯甲醛增强小鼠淋巴因子激活的杀伤细胞的细胞毒性作用
Augmentation of murine lymphokine-activated killer cell cytotoxicity by beta-cyclodextrin-benzaldehyde.
作者信息
Kuroki Y, Ochiai H, Kurokawa M, Niwayama S, Kishimoto C, Tazawa K, Fujimaki M
机构信息
Second Department of Surgery, Toyama Medical and Pharmaceutical University, Japan.
出版信息
J Cancer Res Clin Oncol. 1991;117(2):109-14. doi: 10.1007/BF01613133.
We investigated the effect of beta-cyclodextrin-benzaldehyde (CDBA) on lymphokine-activated killer (LAK) cell activity of spleen cells from normal or RCT(+)H-2(+)-sarcoma-bearing C3H/He mice. CDBA augmented the induction of LAK cytotoxicity in vitro against RCT(+)H-2+ tumor cells by IL-2, whereas the culture with CDBA alone did not. In a LAK cytotoxicity assay in vitro, the augmentative effect of CDBA was strongly exerted against spleen cells originating from 2-week-tumor-bearing mice, rather than those from normal mice or mice that had born tumors for 5 weeks. Such an augmentative effect was not observed against other tumor cells (YAC-1, D-6, Colon-26 and EL-4 cells) non-specifically. When the intravenous adoptive transfer of LAK cells was carried out in the mice, LAK cells from tumor-bearing mice induced by combined culture with interleukin-2 (IL-2) and CDBA markedly inhibited the pulmonary metastases of RCT(+)H-2+ tumor, while neither LAK cells from the same tumor-bearing mice induced by only IL-2 nor those from normal mice inhibited the pulmonary metastasis. The majority of LAK cells induced either by IL-2 plus CDBA or by IL-2 alone were found to be Thy1.2+ and asialoGM1+ cells by flow-cytometric analysis, but no obvious phenotypical difference was observed between them. However, the most significant effect of CDBA might be the maintenance of the Lyt-2+ cell level in the spleen cells from tumor-bearing mice. These results suggested that the costimulation of spleen cells with IL-2 and CDBA might induce cytotoxic T cells specific for syngeneic tumor cells.
我们研究了β-环糊精-苯甲醛(CDBA)对正常或荷RCT(+)H-2(+)肉瘤的C3H/He小鼠脾细胞的淋巴因子激活的杀伤(LAK)细胞活性的影响。CDBA增强了白细胞介素-2(IL-2)在体外对RCT(+)H-2+肿瘤细胞诱导的LAK细胞毒性,而单独用CDBA培养则无此作用。在体外LAK细胞毒性试验中,CDBA的增强作用对来自荷瘤2周小鼠的脾细胞作用强烈,而对正常小鼠或荷瘤5周小鼠的脾细胞作用不明显。对其他肿瘤细胞(YAC-1、D-6、结肠-26和EL-4细胞)未观察到非特异性的增强作用。当在小鼠中进行LAK细胞的静脉内过继转移时,由白细胞介素-2(IL-2)和CDBA联合培养诱导的荷瘤小鼠的LAK细胞显著抑制了RCT(+)H-2+肿瘤的肺转移,而仅由IL-2诱导的同一荷瘤小鼠的LAK细胞或正常小鼠的LAK细胞均未抑制肺转移。通过流式细胞术分析发现,由IL-2加CDBA或仅由IL-2诱导的大多数LAK细胞是Thy1.2+和去唾液酸GM1+细胞,但它们之间未观察到明显的表型差异。然而,CDBA最显著的作用可能是维持荷瘤小鼠脾细胞中Lyt-2+细胞水平。这些结果表明,用IL-2和CDBA对脾细胞进行共刺激可能诱导对同基因肿瘤细胞具有特异性的细胞毒性T细胞。