Fukiage T, Murakami H, Eura M, Ikawa T, Ishikawa T
Department of Otolaryngology, Kumamoto University, School of Medicine, Japan.
Cancer Immunol Immunother. 1991;33(3):139-45. doi: 10.1007/BF01756133.
Peripheral blood lymphocytes were cultured for 5 days with allogeneic tumor cells (allogeneic mixed lymphocyte/tumor cell culture), and subsequently cultured with recombinant interleukin-2 for 12 days. These cultured cells were found to be cytotoxic to autologous tumor cells. Results of two-color analysis using monoclonal antibodies to cell markers showed that more than 80% of their cultured cells were CD3+ cells, and CD4+ cells showed a higher distribution than CD8+ cells. However, CD8+ cells had a much higher killing activity with autologous tumor than did CD4+ cells, when estimated by an elimination study using monoclonal antibodies to T cell phenotypes and complement. The "cold-target" inhibition test showed that the cytotoxicity of these cells for autologous tumor cells was inhibited by unlabeled autologous tumor cells but not by unlabeled stimulator cells. Furthermore, about 40% of the cytotoxicity was suppressed by blocking of HLA class I antigen with a monoclonal antibody on autologous tumor cells. Thus, cytotoxic activity of lymphocytes to autologous tumor restricted by target cell HLA class I antigen is possibly induced by allogeneic tumor-stimulation.
外周血淋巴细胞与异基因肿瘤细胞共培养5天(异基因混合淋巴细胞/肿瘤细胞培养),随后用重组白细胞介素-2培养12天。发现这些培养的细胞对自体肿瘤细胞具有细胞毒性。使用针对细胞标志物的单克隆抗体进行双色分析的结果表明,超过80%的培养细胞为CD3+细胞,且CD4+细胞的分布高于CD8+细胞。然而,当通过使用针对T细胞表型的单克隆抗体和补体的消除研究进行评估时,CD8+细胞对自体肿瘤的杀伤活性比CD4+细胞高得多。“冷靶”抑制试验表明,这些细胞对自体肿瘤细胞的细胞毒性被未标记的自体肿瘤细胞抑制,但未被未标记的刺激细胞抑制。此外,用单克隆抗体阻断自体肿瘤细胞上的HLA I类抗原可抑制约40%的细胞毒性。因此,淋巴细胞对受靶细胞HLA I类抗原限制的自体肿瘤的细胞毒性活性可能是由异基因肿瘤刺激诱导的。