Wehrmaker A, Lehmann V, Dröge W
Cell Immunol. 1986 Sep;101(2):290-8. doi: 10.1016/0008-8749(86)90142-5.
The immunogenicity of a mutagenized subline (ESb-D) of the weakly immunogenic T-cell lymphoma L 5178 Y ESb has been characterized. The injection of 10(6) ESb-D cells ip did not establish lethal tumors in untreated DBA/2 mice but established tumors in sublethally irradiated mice. Injection of ESb-D cells into otherwise untreated DBA/2 mice established also a state of protective immunity against the subsequent injection of otherwise lethal doses of ESb tumor cells. Protection was only obtained after injection of intact but not UV-irradiated or mitomycin-C-treated ESb-D cells. A direct T-cell-mediated cytotoxic activity was also demonstrable in the spleen cells of DBA/2 mice after injection of ESb-D cells but not ESb cells. The cytotoxic activity was variant specific for ESb-D target cells, and it was induced only with intact but not UV-irradiated or mitomycin C-treated ESb-D cells. This suggested that the induction of protective and cytotoxic immunity may require the persistence of the antigen or unusually high antigen doses. The in vivo priming for a secondary in vitro cytotoxic response, in contrast, was achieved with intact and also with mitomycin C-treated ESb-D cells but again not with UV-irradiated ESb-D cells. This indicated that the metabolic activity was a minimal requirement for the in vivo immunogenicity of the ESb-D tumor line. The secondary cytotoxic activity was demonstrable on ESb-D and ESb target cells and could be restimulated in vitro about equally well with ESb-D and ESb cells. But the in vivo priming was again only obtained with ESb-D cells and not with ESb cells. These experiments thus demonstrated that the requirements for immunogenicity are more stringent in vivo than in vitro, and more stringent for the induction of direct cytotoxic and protective immunity in vivo than for the in vivo priming for secondary in vitro responses.
对弱免疫原性的T细胞淋巴瘤L 5178 Y ESb的诱变亚系（ESb-D）的免疫原性进行了表征。腹腔注射10⁶个ESb-D细胞，在未处理的DBA/2小鼠中未形成致死性肿瘤，但在亚致死剂量照射的小鼠中形成了肿瘤。将ESb-D细胞注射到未作其他处理的DBA/2小鼠中，也建立了针对随后注射的致死剂量ESb肿瘤细胞的保护性免疫状态。只有在注射完整的ESb-D细胞而非紫外线照射或丝裂霉素C处理的ESb-D细胞后，才能获得保护作用。在注射ESb-D细胞而非ESb细胞后，DBA/2小鼠的脾细胞中也可证明有直接的T细胞介导的细胞毒性活性。细胞毒性活性对ESb-D靶细胞具有变体特异性，并且仅由完整的而非紫外线照射或丝裂霉素C处理的ESb-D细胞诱导产生。这表明保护性和细胞毒性免疫的诱导可能需要抗原的持续存在或异常高的抗原剂量。相比之下，完整的以及经丝裂霉素C处理的ESb-D细胞均可在体内引发二次体外细胞毒性反应，而紫外线照射的ESb-D细胞则不能。这表明代谢活性是ESb-D肿瘤系体内免疫原性的最低要求。二次细胞毒性活性在ESb-D和ESb靶细胞上均可证明，并且用ESb-D和ESb细胞在体外再次刺激的效果大致相同。但体内引发同样仅用ESb-D细胞获得，而非ESb细胞。因此，这些实验表明，免疫原性的要求在体内比在体外更为严格，并且在体内诱导直接细胞毒性和保护性免疫比在体内引发二次体外反应的要求更为严格。
