Prather S O, Lausch R N
J Immunol. 1977 Jan;118(1):203-10.
Spleen cells obtained from hamsters bearing PARA-7 tumors greater than 1.0 cm were not reactive in microcytotoxicity assays unless preincubated overnight. The events occurring during in vitro incubation which lead to reversal of tumor-mediated suppression of cellular immunity were investigated. After 24 hr of incubation, supernatants overlying spleen cells from tumor-bearing hosts contained a factor which blocked cytotoxicity of simian virus 40 (SV40)3-sensitized spleen cells at the PARA-7 target cell level but not at the effector cell level. The preparations did not mediate antibody-dependent cellular cytotoxicity (ADCC). Opposite results were obtained in assays of culture medium overlying spleen cells from hosts with a tumor burden less than 0.1 cm. Although ADCC activity was present, no significant blocking was detectable. Treatment of inactive spleen cells with anti-hamster gamma-globlin in the presence of complement (anti-HGG + C) prevented activation and formation of blocking factor but did not impair the cytotoxic activity of already activated cells. Addition of SV40 antiserum to anti-HGG + C-treated cells led to effector cell activation, whereas heterologous virus-immune sera did not. Control studies established that the antibody-mediated recovery of cytotoxicity was not due to arming. Further studies showed that PARA-7 tumor antigen extract blocked at the effector cell level, not at the target cell level. Addition of PARA-7 extract to spleen cell supernatants mediating ADCC resulted in formation of a factor which blocked at the target cell level but not at the effector cell level. These data are compatible with the following interpretation. Spleen cell unresponsiveness is due to antigen blockade. Recovery of cytotoxicity occurs because antibody synthesized during the incubation period promotes elution of antigen from the effector cell surface. Thus, activation is accompanied by the generation of tumor antigen-antibody complexes.
从患有直径大于1.0厘米的PARA - 7肿瘤的仓鼠获取的脾细胞，除非预先孵育过夜，否则在微细胞毒性试验中无反应性。对体外孵育期间发生的导致肿瘤介导的细胞免疫抑制逆转的事件进行了研究。孵育24小时后，荷瘤宿主脾细胞上的上清液含有一种因子，该因子在PARA - 7靶细胞水平阻断猿猴病毒40（SV40）致敏的脾细胞的细胞毒性，但在效应细胞水平则不然。这些制剂不介导抗体依赖性细胞毒性（ADCC）。在肿瘤负荷小于0.1厘米的宿主的脾细胞上的培养基检测中得到了相反的结果。虽然存在ADCC活性，但未检测到明显的阻断作用。在补体存在的情况下用抗仓鼠γ球蛋白处理无活性的脾细胞（抗HGG + C）可阻止阻断因子的激活和形成，但不损害已激活细胞的细胞毒性活性。向抗HGG + C处理的细胞中加入SV40抗血清可导致效应细胞激活，而异源病毒免疫血清则不然。对照研究确定抗体介导的细胞毒性恢复不是由于武装作用。进一步研究表明，PARA - 7肿瘤抗原提取物在效应细胞水平阻断，而不是在靶细胞水平。将PARA - 7提取物添加到介导ADCC的脾细胞上清液中导致形成一种在靶细胞水平阻断但在效应细胞水平不阻断的因子。这些数据符合以下解释。脾细胞无反应性是由于抗原阻断。细胞毒性的恢复是因为孵育期间合成的抗体促进了抗原从效应细胞表面洗脱。因此，激活伴随着肿瘤抗原 - 抗体复合物的产生。
