Giorgi J V, Warner N L
Int J Cancer. 1983 Nov 15;32(5):629-35. doi: 10.1002/ijc.2910320518.
Previous studies have clearly established that murine plasmacytomas suppress B-cell responses, but no effects on T-cell responses have been noted by most investigators. However, in our investigation of the tumor-associated antigens of plasmacytomas, we have found that immunosuppression plays an important role in the complex interaction between host immune T cells and tumor cells. In these investigations, varying the number of plasmacytoma cells added to in vitro induction systems separated two different effects which these cells had on the generation of cytotoxic T cells. On the one hand, when appropriate numbers were present, tumor cells acted as immunogens and stimulated the generation of specific killer cells against tumor-associated antigen or alloantigen which they expressed. In contrast, greater numbers of tumor cells exerted a profound inhibitory effect on the generation of cytotoxic activity when cells inactivated with irradiation were used. Mitomycin-C inactivation of plasmacytoma cells abrogated this inhibitory activity. In further experiments, MPC-II cells that had been inactivated with Mitomycin C were able to prime T cells in vivo, whereas priming by live tumor cells could not be detected in the same situation. It is suggested that immunosuppression by the live tumor cells may account for their inability to prime T cells in vivo. These results indicate that immunosuppression by plasmacytomas may be one of the important variables which influence the generation of cytotoxic T cells against tumor-associated antigens both in vivo and in vitro.
以往的研究已明确证实,鼠浆细胞瘤会抑制B细胞反应,但大多数研究者并未注意到其对T细胞反应有任何影响。然而,在我们对浆细胞瘤肿瘤相关抗原的研究中,我们发现免疫抑制在宿主免疫T细胞与肿瘤细胞之间的复杂相互作用中起着重要作用。在这些研究中,改变添加到体外诱导系统中的浆细胞瘤细胞数量,分离出了这些细胞对细胞毒性T细胞生成的两种不同影响。一方面,当存在适当数量的肿瘤细胞时,它们作为免疫原起作用,刺激针对它们所表达的肿瘤相关抗原或同种异体抗原产生特异性杀伤细胞。相反,当使用经辐射灭活的细胞时,大量肿瘤细胞对细胞毒性活性的产生具有深远的抑制作用。用丝裂霉素-C使浆细胞瘤细胞失活可消除这种抑制活性。在进一步的实验中,经丝裂霉素C失活的MPC-II细胞能够在体内启动T细胞,而在相同情况下未检测到活肿瘤细胞启动T细胞。提示活肿瘤细胞的免疫抑制作用可能是其在体内无法启动T细胞的原因。这些结果表明,浆细胞瘤的免疫抑制可能是影响体内和体外针对肿瘤相关抗原的细胞毒性T细胞生成的重要变量之一。