Campbell M J, Esserman L, Byars N E, Allison A C, Levy R
Stanford University School of Medicine, Department of Medicine, CA 94306.
J Immunol. 1990 Aug 1;145(3):1029-36.
The roles of humoral and cellular antitumor immune responses induced by immunization with tumor-derived idiotypic IgM were studied in a syngeneic, transplantable B cell lymphoma (38C13) of C3H mice. Id vaccination with keyhole limpet hemocyanin-conjugated Id induced protection against a subsequent lethal tumor challenge. Such immunizations elicited anti-idiotypic antibodies that were cytotoxic in in vitro antibody-dependent cellular cytotoxicity assays as well as in vivo passive transfer experiments. L3T4+ T cells, which proliferated in vitro in response to the specific Id protein, were also induced. However, cells mediating direct cytotoxicity, either in vitro or in vivo, were not observed in the lymph nodes, spleens, or peritoneal cavity of immune mice or at the site of tumor regression as demonstrated by using a tumor sponge implantation model. In addition, in vitro sensitization of immune lymphocytes against 38C13 tumor cells failed to induce cytotoxicity. Immunization with lipid conjugated Id also elicited a T cell proliferative response but failed to induce anti-idiotypic antibodies and did not confer resistance to tumor growth. These results suggest that anti-idiotypic antibodies play the major role in the destruction of 38C13 tumor cells. However, in vivo depletion of L3T4+ or Lyt-2+ cells from 38C-Id-keyhole limpet hemocyanin-immunized mice resulted in diminished protection against a tumor challenge. Thus, although humoral responses appear to play the predominant part in tumor destruction, cellular responses are also required for the full expression of antitumor immunity in this system.
在C3H小鼠的同基因、可移植B细胞淋巴瘤（38C13）中，研究了用肿瘤衍生的独特型IgM免疫诱导的体液和细胞抗肿瘤免疫反应的作用。用钥孔戚血蓝蛋白偶联的独特型进行独特型疫苗接种可诱导对随后致死性肿瘤攻击的保护作用。这种免疫接种引发了抗独特型抗体，这些抗体在体外抗体依赖性细胞毒性试验以及体内被动转移实验中具有细胞毒性。还诱导了L3T4 + T细胞，它们在体外对特异性独特型蛋白产生增殖反应。然而，通过肿瘤海绵植入模型证明，在免疫小鼠的淋巴结、脾脏或腹腔中，或在肿瘤消退部位，均未观察到在体外或体内介导直接细胞毒性的细胞。此外，免疫淋巴细胞对38C13肿瘤细胞的体外致敏未能诱导细胞毒性。用脂质偶联的独特型进行免疫接种也引发了T细胞增殖反应，但未能诱导抗独特型抗体，也未赋予对肿瘤生长的抗性。这些结果表明，抗独特型抗体在38C13肿瘤细胞的破坏中起主要作用。然而，从38C - 独特型 - 钥孔戚血蓝蛋白免疫的小鼠体内清除L3T4 +或Lyt - 2 +细胞会导致对肿瘤攻击的保护作用减弱。因此，尽管体液反应似乎在肿瘤破坏中起主要作用，但在该系统中，细胞反应对于抗肿瘤免疫的充分表达也是必需的。
