Degiovanni G, Lahaye T, Hérin M, Hainaut P, Boon T
Laboratoire de Chirurgie Expérimentale, Université de Liège, Belgium.
Eur J Immunol. 1988 May;18(5):671-6. doi: 10.1002/eji.1830180503.
Peripheral blood lymphocytes from a melanoma patient were stimulated with autologous melanoma cells in mixed lymphocyte tumor cultures (MLTC). After three restimulations, the lytic activity of the responder cells directed against the autologous melanoma cells was higher than that against K-562 and autologous Epstein-Barr virus-transformed B cell line (EBV-B) cells. From these MLTC-responder cells, we derived specific cytolytic T cell (CTL) clones that lysed the autologous melanoma cells and did not lyse K-562 or autologous EBV-B cells. Autologous melanoma clones were found that were resistant to some or all of these CTL clones. The autologous CTL clones recognized at least two different antigens (A, B) on the melanoma cells and three types of melanoma clones could be distinguished (A+B+, A+B-, A-B-). This antigenic heterogeneity of melanoma clones was confirmed by testing the CTL clones in cold target competition and also in antigen-dependent CTL proliferation assays performed with very small numbers of stimulator cells. The data further indicated an instability of the expression of a melanoma-associated antigen in the course of a long culture period. Among the melanoma clones that expressed antigen A, one was found to stimulate the proliferation of anti-A CTL clones much more effectively than the others. This represents a new type of heterogeneity among tumor cells which may be of significance for the elicitation of an autologous anti-tumoral immune response.
在混合淋巴细胞肿瘤培养物（MLTC）中，用来自一名黑色素瘤患者的自体黑色素瘤细胞刺激外周血淋巴细胞。经过三次再刺激后，应答细胞针对自体黑色素瘤细胞的裂解活性高于针对K-562和自体爱泼斯坦-巴尔病毒转化的B细胞系（EBV-B）细胞的裂解活性。从这些MLTC应答细胞中，我们获得了特异性细胞毒性T细胞（CTL）克隆，这些克隆可裂解自体黑色素瘤细胞，但不能裂解K-562或自体EBV-B细胞。发现自体黑色素瘤克隆对部分或所有这些CTL克隆具有抗性。自体CTL克隆识别黑色素瘤细胞上至少两种不同的抗原（A、B），并且可以区分三种类型的黑色素瘤克隆（A+B+、A+B-、A-B-）。通过在冷靶竞争试验以及使用极少量刺激细胞进行的抗原依赖性CTL增殖试验中测试CTL克隆，证实了黑色素瘤克隆的这种抗原异质性。数据进一步表明，在长时间培养过程中，黑色素瘤相关抗原的表达不稳定。在表达抗原A的黑色素瘤克隆中，发现其中一个比其他克隆更有效地刺激抗A CTL克隆的增殖。这代表了肿瘤细胞之间一种新型的异质性，可能对引发自体抗肿瘤免疫反应具有重要意义。
