Takikawa O, Oku T, Yasui H, Yoshida R
Department of Cell Biology, Osaka Bioscience Institute, Japan.
J Immunol. 1993 Aug 15;151(4):2070-6.
Soluble effector molecules involved in the rejection of allografted mouse Meth A (3-methylcholanthrene-induced ascites type tumor) cells were examined. A potent antiproliferative activity against the tumor cells was detected in the culture supernatant of leukocytes that had infiltrated into the peritoneal cavity of C57BL/6 mice on days 6-8 after transplantation, when the i.p. transplanted Meth A cells were undergoing rejection. Studies with neutralizing antibodies indicated that both IFN-gamma and IL-1 alpha/beta were required for the activity but that TNF-alpha was not. Actually, mouse rIFN-gamma and rIL-1 alpha/beta used, at the concentrations found in the culture supernatant determined by ELISA, were able to reconstitute the potent antiproliferative activity, although each cytokine alone had a weak growth inhibitory activity against Meth A cells. The half-maximal inhibition was observed with 0.02-0.03 U/ml of rIL-1 alpha/beta at 1-100 U/ml of rIFN-gamma. The synergistic growth inhibitory effect of these cytokines also was observed with four of 15 mouse transformed cell lines tested, indicating that the effect was not specific to Meth A cells. These findings suggest that IFN-gamma and IL-1 alpha/beta participate as soluble effector molecules in the rejection of some allografted tumor cells including Meth A cells.
对参与同种异体移植小鼠Meth A（3-甲基胆蒽诱导的腹水型肿瘤）细胞排斥反应的可溶性效应分子进行了检测。在移植后第6至8天，当腹腔内移植的Meth A细胞正在被排斥时，浸润到C57BL/6小鼠腹腔的白细胞培养上清液中检测到了对肿瘤细胞的强大抗增殖活性。用中和抗体进行的研究表明，该活性需要IFN-γ和IL-1α/β两者，但不需要TNF-α。实际上，以ELISA测定的培养上清液中发现的浓度使用的小鼠重组IFN-γ和重组IL-1α/β能够重建强大的抗增殖活性，尽管每种细胞因子单独对Meth A细胞只有微弱的生长抑制活性。在1-100 U/ml的rIFN-γ存在下，0.02-0.03 U/ml的rIL-1α/β可观察到半数最大抑制。在测试的15种小鼠转化细胞系中的4种中也观察到了这些细胞因子的协同生长抑制作用，表明该作用并非Meth A细胞所特有。这些发现表明，IFN-γ和IL-1α/β作为可溶性效应分子参与了包括Meth A细胞在内的一些同种异体移植肿瘤细胞的排斥反应。
