Somasundaram Rajasekharan, Caputo Laura, Guerry DuPont, Herlyn Dorothee
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
J Transl Med. 2005 Nov 10;3:41. doi: 10.1186/1479-5876-3-41.
A CD8+ cytotoxic T lymphocyte (CTL) line was derived from the peripheral blood mononuclear cells of a patient with primary melanoma. The CD8+ CTL line specifically lysed the autologous primary melanoma cells and not the natural killer cell-sensitive K562 cells or lymphokine activated killer cell-sensitive DAUDI cells. When a large panel of human leukocyte antigen (HLA)-matched and -unmatched allogeneic melanoma, glioma, breast and colorectal carcinoma cells was tested as targets in cytolysis assays, 4 HLA-matched and two HLA-unmatched allogeneic metastatic melanoma lines were lysed by the CD8+ CTL. Lysis of autologous and allogeneic melanoma cells was dependent on the effector-to-target cell ratio. Lysis of autologous melanoma cells was not blocked by anti-HLA class I or class II antibodies, confirming that the cytolytic activity of the CD8+ CTL was HLA-unrestricted. CTL lysis of autologous melanoma cells was CD3 (T cell receptor) dependent and FAS-FAS-L, and CD1 independent. Identification of the melanoma-associated antigen recognized by the HLA-unrestricted CTL may provide a vaccine for a broad population of melanoma patients.
一个CD8 + 细胞毒性T淋巴细胞(CTL)系源自一名原发性黑色素瘤患者的外周血单个核细胞。该CD8 + CTL系特异性裂解自体原发性黑色素瘤细胞,而不裂解自然杀伤细胞敏感的K562细胞或淋巴因子激活的杀伤细胞敏感的DAUDI细胞。当在细胞溶解试验中测试一大组人类白细胞抗原(HLA)匹配和不匹配的同种异体黑色素瘤、神经胶质瘤、乳腺癌和结肠癌细胞作为靶标时,4个HLA匹配和2个HLA不匹配的同种异体转移性黑色素瘤系被CD8 + CTL裂解。自体和同种异体黑色素瘤细胞的裂解取决于效应细胞与靶细胞的比例。抗HLA I类或II类抗体不能阻断自体黑色素瘤细胞的裂解,证实CD8 + CTL的细胞溶解活性不受HLA限制。CD8 + CTL对自体黑色素瘤细胞的裂解依赖于CD3(T细胞受体),且与FAS - FAS - L和CD1无关。鉴定HLA非限制性CTL识别的黑色素瘤相关抗原可能为广大黑色素瘤患者提供一种疫苗。