Nakanishi M, Kan N, Okino T, Satoh K, Mise K, Teramura Y, Yamasaki S, Ohgaki K, Tobe T
First Department of Surgery, School of Medicine, Kyoto University, Japan.
Biotherapy. 1990;2(1):21-32. doi: 10.1007/BF02172073.
Peripheral blood lymphocytes, regional lymph node lymphocytes or malignant effusion lymphocytes from cancer patients were incubated with crude IL-2 (cIL-2) for 13 days. These effectors, which frequently expressed IL-2 receptor (IL-2R), proliferated well and possessed augmented killing activity against fresh autologous tumor cells and K562. However, when recombinant IL-2 (rIL-2) was added for the last 4 days of culture instead of cIL-2, IL-2R expression and killing activity against fresh autologous tumor cells decreased significantly (P less than 0.05). Phenotypic analysis indicated that cIL-2 significantly promoted the expansion of the cytotoxic population (CD8+.11b-)(P less than 0.05). The decreases in killing activity and IL-2R expression were restored by 0.004% PHA plus rIL-2, but not in the presence of rIFN-gamma, rIL-1 alpha, rIL-1 beta, rIL-4 or rIL-6. PHA-free cIL-2 maintained killing activity, but not IL-2R expression. We conclude that some factors in cIL-2 and a low dose of PHA-P are necessary for the maintenance of killing activity and IL-2R expression of cultured lymphocytes in the late phase of culture.
将癌症患者的外周血淋巴细胞、区域淋巴结淋巴细胞或恶性积液淋巴细胞与粗制白细胞介素-2(cIL-2)一起孵育13天。这些效应细胞经常表达白细胞介素-2受体(IL-2R),增殖良好,对新鲜自体肿瘤细胞和K562具有增强的杀伤活性。然而,当在培养的最后4天添加重组白细胞介素-2(rIL-2)而非cIL-2时,IL-2R表达以及对新鲜自体肿瘤细胞的杀伤活性显著降低(P小于0.05)。表型分析表明,cIL-2显著促进细胞毒性群体(CD8 +.11b -)的扩增(P小于0.05)。杀伤活性和IL-2R表达的降低可通过0.004%的PHA加rIL-2恢复,但在存在rIFN-γ、rIL-1α、rIL-1β、rIL-4或rIL-6时则不能恢复。不含PHA的cIL-2可维持杀伤活性,但不能维持IL-2R表达。我们得出结论,cIL-2中的某些因子和低剂量的PHA-P对于培养后期淋巴细胞杀伤活性和IL-2R表达的维持是必要的。