Fuji H, Mihich E
Cancer Res. 1975 Apr;35(4):946-52.
The immunogenicity of lymphoma L1210 and three L1210 sublines, resistant to methylglyoxal bis(guanylhydrazone), 4,4'-diacetyldiphenylurea bis(guanylhydrazone), or guanazole (L1210/GZL), respectively, was evaluated. Syngeneic DBA/2J mice were given a single i.p. injection of serially diluted suspension of irradiated cells from L1210 or L1210 sublines. Five days later spleen cells from the immunized mice were tested for the presence of plaque-forming cells using the immunizing lymphoma cell lines as target. Sera collected from the animals were examined for cytolytic antibody activity by lysis in gel using the same target cells. For comparison, the H-2 immunogenicity of L1210 and its sublines was investigated in H-2-incompatible allogeneic mice. The following results were obtained. (a) All the sublines showed increased immunogenicity and susceptibility to lysis as compared to L1210 cells. The number of plaque-forming cells/spleen ranged from 100 for L1210 to 4450 for L1210/GZL, the most immunogenic subline, and the antibody titer ranged from 1/8 for L1210 to 1/128 for L1210/GZL. (b) All the sublines carried common tumor-associated antigens that apparently made primary contributions to the increased immunogenicity. (c) The common tumor-associated antigens were also expressed on L1210 cells, although in a lesser defree, as evidenced by the definite, albeit low, capacity of L1210 cells to absorb DBA/2J anti-L1210/GZL antibodies. (d) Spleen and thymus cells of DBA/2J mice as well as unrelated murine ascites tumor cells did not cause significant absorption of these antibodies. (e) Only a partial inverse relationship could be demonstrated between tumor-associated antigens but the lowest for H-2. The above results would seem compatible with the hypothesis that the increased immunogenicity of drug-resistant L1210 sublines is attributable to the selection of preexisting highly immunogenic cells during immunosuppression by treatments selecting for drug resistance.
评估了淋巴瘤L1210及其三个分别对甲基乙二醛双（胍腙）、4,4'-二乙酰二苯基脲双（胍腙）或胍唑具有抗性的L1210亚系（L1210/GZL）的免疫原性。同基因DBA/2J小鼠经腹腔单次注射经辐照的L1210或L1210亚系细胞的系列稀释悬浮液。五天后，以免疫所用的淋巴瘤细胞系为靶细胞，检测免疫小鼠脾脏细胞中是否存在噬斑形成细胞。用相同的靶细胞通过凝胶中的裂解作用检测从动物收集的血清中的溶细胞抗体活性。为作比较，在H-2不相容的同种异体小鼠中研究了L1210及其亚系的H-2免疫原性。获得了以下结果。（a）与L1210细胞相比，所有亚系均表现出免疫原性增加以及对裂解的敏感性增加。每脾脏噬斑形成细胞的数量范围从L1210的100个到免疫原性最强的亚系L1210/GZL的4450个，抗体效价范围从L1210的1/8到L1210/GZL的1/128。（b）所有亚系都携带共同的肿瘤相关抗原，这些抗原显然对免疫原性的增加起主要作用。（c）共同的肿瘤相关抗原也在L1210细胞上表达，尽管程度较低，这由L1210细胞明确（尽管很低）的吸收DBA/2J抗L1210/GZL抗体的能力所证明。（d）DBA/2J小鼠的脾脏和胸腺细胞以及无关的鼠腹水肿瘤细胞均未引起这些抗体的显著吸收。（e）肿瘤相关抗原之间仅能证明存在部分反比关系，但H-2相关的反比关系最低。上述结果似乎与以下假设相符，即耐药L1210亚系免疫原性增加归因于在通过选择耐药性的处理进行免疫抑制期间对预先存在的高免疫原性细胞的选择。
