Wallach D
J Immunol. 1984 May;132(5):2464-9.
Preparations of human lymphotoxins (LT) were effectively cytotoxic to HeLa cells when applied in the presence of cycloheximide (CHI). In the absence of CHI, however, they failed to cause any cell death. Moreover, LT applied in the absence of CHI induced resistance that was reflected in decreased vulnerability to subsequent incubation with LT in the presence of CHI. This induction of resistance to LT, in treating cells with preparations of LT, was quite rapid, reaching its maximal extent within 2 hr of LT application. It could also be observed in cells of other cultured human lines besides HeLa (SV80 and WISH), and the range of LT concentrations at which it was observed was similar to that at which death of cells was induced by LT in the presence of CHI. In fractionating LT preparations on DEAE cellulose, the resistance inducing activity appeared to co-purify with the cytotoxic activity, suggesting that both activities reside in the same molecule. We suggest that LT, or some lymphokines that are formed by lymphocytes concomitantly with the formation of LT, can induce cellular mechanisms that interfere with the cytotoxic activity of LT and that CHI makes the cell sensitive to the cytotoxicity of LT by reducing the activity of these protective mechanisms. This kind of negative feedback regulation in the function of LT might contribute to selectivity in their action.
当在放线菌酮（CHI）存在的情况下应用时，人淋巴毒素（LT）制剂对HeLa细胞具有有效的细胞毒性。然而，在没有CHI的情况下，它们未能导致任何细胞死亡。此外，在没有CHI的情况下应用的LT诱导了抗性，这表现为在随后在CHI存在的情况下与LT孵育时对其敏感性降低。在用LT制剂处理细胞时，这种对LT抗性的诱导相当迅速，在应用LT后2小时内达到最大程度。在除HeLa（SV80和WISH）之外的其他培养的人细胞系中也可以观察到这种现象，并且观察到抗性诱导的LT浓度范围与在CHI存在的情况下LT诱导细胞死亡的浓度范围相似。在用DEAE纤维素对LT制剂进行分级分离时，抗性诱导活性似乎与细胞毒性活性共纯化，这表明两种活性存在于同一分子中。我们认为，LT或一些与LT形成同时由淋巴细胞形成的淋巴因子，可以诱导干扰LT细胞毒性活性的细胞机制，并且CHI通过降低这些保护机制的活性使细胞对LT的细胞毒性敏感。LT功能中的这种负反馈调节可能有助于其作用的选择性。
