Vose B M, White W
Cancer Immunol Immunother. 1983;15(3):227-36. doi: 10.1007/BF00199170.
Lymphocytes from cancer patients were stimulated in mixed culture with autologous tumour (MLTC) or pooled allogeneic lymphocytes (MLC). Both protocols induced increased uptake of 3H-thymidine at 5 days and the appearance of lymphoblasts. Blasts were isolated on discontinuous Percoll gradients and either expanded as bulk cultures or cloned directly under limiting dilution conditions in the presence of conditioned medium containing IL-2. Results with MLTC-blast-CTC have been reported elsewhere. MLC-activated cultures lysed autologous tumour but not autologous lymphoblasts. Lysis of some allogeneic tumours, lymphoblasts from members of the inducing pool, and K562 was also apparent. MLC activated cultures did not undergo restimulation in response to autologous tumour or lymphocytes but were restimulated by leukocytes from pool members. MLTC clones showed autologous tumour-specific cytotoxic activity or cross-reactive proliferative responses with tumours of the same site and histology. The majority of MLC clones cytotoxic for autologous tumour were also specific and did not lyse allogeneic tumour, K562, or lymphoblasts from the inducing pool. Two clones lysed autologous tumour and pool members. None of the clones tested proliferated in response to autologous tumour following MLC activation but some were responsive to pool members and one clone was restimulated by autologous monocytes. No association was found between clone phenotype and function. The implication of these data is that the effector cells with activity against autologous tumour induced in MLC arose largely by transstimulation of in vivo-activated tumour reactive lymphocytes by IL-2 release rather than expansion of NK-like effectors or sharing of antigenic specificities between tumour and allogeneic lymphocytes. Since MLC activation of cancer patients lymphocytes does not induce proliferative responses to autologous tumour it is unlikely to be a useful procedure in preparing cells for immunotherapy protocols.
将癌症患者的淋巴细胞与自体肿瘤进行混合培养（MLTC）或与汇集的同种异体淋巴细胞进行混合培养（MLC）。两种方案均在第5天诱导3H-胸腺嘧啶核苷摄取增加以及淋巴母细胞的出现。通过不连续的Percoll梯度分离母细胞，并在含有IL-2的条件培养基存在下，作为批量培养物进行扩增或直接在有限稀释条件下进行克隆。关于MLTC-母细胞-CTC的结果已在其他地方报道。MLC激活的培养物可裂解自体肿瘤，但不能裂解自体淋巴母细胞。对一些同种异体肿瘤、诱导池成员的淋巴母细胞以及K562的裂解也很明显。MLC激活的培养物不会因自体肿瘤或淋巴细胞而发生再次刺激，但会被来自池成员的白细胞再次刺激。MLTC克隆显示出对自体肿瘤的特异性细胞毒性活性或与相同部位和组织学的肿瘤的交叉反应性增殖反应。大多数对自体肿瘤具有细胞毒性的MLC克隆也是特异性的，不会裂解同种异体肿瘤、K562或诱导池中的淋巴母细胞。两个克隆可裂解自体肿瘤和池成员。在MLC激活后，所测试的克隆均未因自体肿瘤而增殖，但有些对池成员有反应，一个克隆被自体单核细胞再次刺激。未发现克隆表型与功能之间存在关联。这些数据的含义是，在MLC中诱导产生的针对自体肿瘤具有活性的效应细胞很大程度上是通过IL-2释放对体内激活的肿瘤反应性淋巴细胞进行转刺激而产生的，而不是NK样效应细胞的扩增或肿瘤与同种异体淋巴细胞之间抗原特异性的共享。由于癌症患者淋巴细胞的MLC激活不会诱导对自体肿瘤的增殖反应，因此它不太可能是为免疫治疗方案制备细胞的有用方法。
