Kuge S, Watanabe K, Makino K, Tokuda Y, Mitomi T, Kawamura N, Habu S, Nishimura T
Department of Immunology, Tokai University School of Medicine, Isehara.
Jpn J Cancer Res. 1995 Feb;86(2):135-9. doi: 10.1111/j.1349-7006.1995.tb03030.x.
Human tumor-infiltrating lymphocytes (TIL) were obtained from breast cancer, renal cancer or neuroblastoma to investigate the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes (CTL). When TIL were cultured with interleukin (IL)-2 (100 U/ml), the growth of TIL peaked around 8-10 days after the initiation of culture. In contrast, the proliferation of TIL cultured with IL-2 plus IL-12 peaked around 4-5 days after culture and tumor cells rapidly disappeared from the culture. To determine the generation of autologous tumor-reactive CD8+ CTL, TIL-derived CD8+ T cells were separated by FACStar. Both IL-2-activated and IL-2 plus IL-12-activated TIL-CD8+ T cells showed the same level of lymphokine-activated killer activity against a variety of tumor cells. However, TIL-CD8+ T cells activated with IL-2 plus IL-12 revealed greatly augmented cytotoxicity against autologous tumor cells compared with that induced by IL-2 alone. The autologous tumor cell-killing activity of TIL-CD8+ CTL was significantly inhibited by the addition of F(ab)2 anti-CD3 monoclonal antibody, indicating that these CTL recognize autologous tumor antigen through T cell receptor. These results imply that IL-12 is a novel cytokine which facilitates the generation of autologous tumor-reactive CD8+ CTL from TIL.
从乳腺癌、肾癌或神经母细胞瘤中获取人肿瘤浸润淋巴细胞（TIL），以研究自体肿瘤反应性CD8 + 细胞毒性T淋巴细胞（CTL）的产生。当TIL与白细胞介素（IL）-2（100 U/ml）一起培养时，TIL的生长在培养开始后约8 - 10天达到峰值。相比之下，用IL-2加IL-12培养的TIL增殖在培养后约4 - 5天达到峰值，并且肿瘤细胞迅速从培养物中消失。为了确定自体肿瘤反应性CD8 + CTL的产生，通过FACStar分离TIL来源的CD8 + T细胞。IL-2激活的和IL-2加IL-12激活的TIL-CD8 + T细胞对多种肿瘤细胞均表现出相同水平的淋巴因子激活的杀伤活性。然而，与单独使用IL-2诱导的相比，用IL-2加IL-12激活的TIL-CD8 + T细胞对自体肿瘤细胞的细胞毒性大大增强。加入F(ab)2抗CD3单克隆抗体可显著抑制TIL-CD8 + CTL的自体肿瘤细胞杀伤活性，表明这些CTL通过T细胞受体识别自体肿瘤抗原。这些结果表明，IL-12是一种新型细胞因子，可促进从TIL中产生自体肿瘤反应性CD8 + CTL。
