Mokyr M B, Ye Q W
Cancer Res. 1985 Oct;45(10):4932-9.
We have shown previously (Ye, Q-W., and Mokyr, M. B. Cancer Res., 44: 3873-3879, 1984) that, following low-dose cyclophosphamide (CY) therapy (15 mg/kg) of mice bearing a large s.c. MOPC-315 tumor and extensive metastases, T-cell-dependent immunopotentiating activity appears in their hitherto immunosuppressive Sephadex G-10-adherent spleen cell population. Here we show that the CY-induced immunopotentiating T-cells express the Lyt 1, Lyt 2, and L3T4 phenotypes. The phenotype of the immunopotentiating T-cells was deduced from our observations that depletion of Lyt 1+, Lyt 2+, or L3T4+ cells from the Sephadex G-10-adherent spleen cell population of CY-treated tumor bearers abolished the ability of the adherent cells to enhance the generation of antitumor cytotoxicity when added to the in vitro immunization culture of normal spleen cells. Moreover, admixture of a Sephadex G-10-adherent cell population depleted of Lyt 2+ cells with a Sephadex G-10-adherent cell population depleted of L3T4+ cells failed to restore the immunopotentiating activity, indicating that T-cells that are apparently expressing simultaneously the Lyt 2 and L3T4 antigens are required for the exertion of the CY-induced immunopotentiating activity. The CY-induced immunopotentiating T-cells from MOPC-315 tumor bearers brought about the appearance of enhanced antitumor cytotoxicity not only against the MOPC-315 tumor cells, but also against two other syngeneic plasmacytomas, with surface immunoglobulin of a different class and antigenic specificity than the MOPC-315 tumor cells, as well as against a variant MOPC-315 tumor line which lacks surface immunoglobulin. The CY-induced immunopotentiating T-cells did not enhance the appearance of antitumor cytotoxicity against a syngeneic (WEHI 22.1) or an allogeneic (EL4) tumor of T-cell origin nor against the natural killer-sensitive YAC-1 cells. Thus, L3T4+, Lyt2+ T-cells from CY-treated MOPC-315 tumor bearers enhance the generation of antitumor cytotoxicity that is directed against plasmacytoma shared antigens other than immunoglobulins.
我们先前已经表明（Ye, Q-W.和Mokyr, M. B. 《癌症研究》，44: 3873 - 3879, 1984），对患有大型皮下MOPC - 315肿瘤并伴有广泛转移的小鼠进行低剂量环磷酰胺（CY）治疗（15 mg/kg）后，其原本具有免疫抑制作用的葡聚糖凝胶G - 10黏附脾细胞群体中会出现T细胞依赖性免疫增强活性。在此我们表明，CY诱导的免疫增强T细胞表达Lyt 1、Lyt 2和L3T4表型。免疫增强T细胞的表型是从我们的观察结果推导出来的，即从接受CY治疗的肿瘤携带者的葡聚糖凝胶G - 10黏附脾细胞群体中去除Lyt 1 +、Lyt 2 +或L3T4 +细胞后，当将这些黏附细胞添加到正常脾细胞的体外免疫培养中时，它们增强抗肿瘤细胞毒性产生的能力就会丧失。此外，将去除Lyt 2 +细胞的葡聚糖凝胶G - 10黏附细胞群体与去除L3T4 +细胞的葡聚糖凝胶G - 10黏附细胞群体混合，无法恢复免疫增强活性，这表明明显同时表达Lyt 2和L3T4抗原的T细胞是发挥CY诱导的免疫增强活性所必需的。来自MOPC - 315肿瘤携带者的CY诱导的免疫增强T细胞不仅使针对MOPC - 315肿瘤细胞的抗肿瘤细胞毒性增强，而且还使针对另外两种同基因浆细胞瘤的抗肿瘤细胞毒性增强，这两种浆细胞瘤的表面免疫球蛋白类别和抗原特异性与MOPC - 315肿瘤细胞不同，以及针对一种缺乏表面免疫球蛋白的MOPC - 315肿瘤变异株。CY诱导的免疫增强T细胞并没有增强针对同基因（WEHI 22.1）或异基因（EL4）T细胞源性肿瘤以及针对自然杀伤敏感的YAC - 1细胞的抗肿瘤细胞毒性的出现。因此，来自接受CY治疗的MOPC - 315肿瘤携带者的L3T4 +、Lyt2 + T细胞增强了针对除免疫球蛋白以外的浆细胞瘤共享抗原的抗肿瘤细胞毒性的产生。
