Saito T, Ruffman R, Welker R D, Herberman R B, Chirigos M A
Cancer Immunol Immunother. 1985;19(2):130-5. doi: 10.1007/BF00199721.
Four biological response modifiers (BRMs), MVE-2 (maleic anhydride divinyl ether), Corynebacterium parvum (C. Parvum), PolyICLC (polyinosinic:polycytidylic acid stabilized with poly-L-lysine), and mouse alpha beta-interferon (alpha beta-IFN), were tested to assess whether repeated treatments would repeatedly induce or sustain augmented levels of natural killer (NK) cell activity and/or macrophage (M0)-mediated inhibition of tumor cell growth. In contrast to a significant increase in splenic NK activity obtained with a single treatment with each of the agents, multiple treatments with these BRMs led to a progressive decrease in the degree of augmentation of NK activity. In contrast, multiple injections with these agents resulted in sustained augmentation of M0-mediated reactivity. Separation of the spleen cells by Percoll discontinuous density gradient centrifugation indicated that with mice treated once with each BRM high levels of NK activity were detected in the lower density fractions and that these fractions contained a higher percentage of large granular lymphocytes (LGLs) than that found in comparable fractions from normal mice. In contrast, cells in the lower density fractions from mice that received multiple treatments had decreased NK activity and an appreciably lower proportion of LGLs. These results indicate that the development of hyporesponsiveness to augmentation of splenic NK-cell activity following multiple treatments with BRMs may be attributable to a decreased percentage of LGLs, the effector cell population responsible for NK cell-mediated cytotoxicity.
对四种生物反应调节剂（BRM），即MVE-2（马来酸酐二乙烯基醚）、短小棒状杆菌（C. Parvum）、聚肌胞苷酸（聚肌苷酸:聚胞苷酸与聚-L-赖氨酸稳定结合）和小鼠αβ干扰素（αβ-IFN）进行了测试，以评估重复治疗是否会反复诱导或维持自然杀伤（NK）细胞活性增强水平和/或巨噬细胞（M0）介导的肿瘤细胞生长抑制。与单次使用每种药物后脾脏NK活性显著增加相反，用这些BRM进行多次治疗导致NK活性增强程度逐渐降低。相反，多次注射这些药物导致M0介导的反应持续增强。通过Percoll不连续密度梯度离心分离脾细胞表明，用每种BRM单次处理的小鼠，在较低密度组分中检测到高水平的NK活性，并且这些组分中含有比正常小鼠相应组分中更高百分比的大颗粒淋巴细胞（LGL）。相反，接受多次治疗的小鼠较低密度组分中的细胞NK活性降低，LGL比例明显较低。这些结果表明，用BRM多次治疗后对脾脏NK细胞活性增强反应性降低的发生可能归因于LGL百分比的降低，LGL是负责NK细胞介导的细胞毒性的效应细胞群体。
