LONG-TERM CULTURE OF TUMOR-SPECIFIC CYTOTOXIC T-CELLS
LONG-TERM CULTURE OF TUMOR-SPECIFIC CYTOTOXIC T-CELLS
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DOI：
10.1038/268154a0
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发表时间：
1977-01-01
期刊：
影响因子：
64.8
通讯作者：
SMITH, KA
中科院分区：
文献类型：
--
作者：
GILLIS, S;SMITH, KA
许多研究者已经成功地维持了人骨髓源性（B）细胞的长期组织培养。这些细胞系是从正常受试者1和淋巴组织增生性疾病患者2中建立的。在大多数情况下，长期B细胞系已被证明含有EB病毒基因组，一些研究人员认为这是建立和维持长期培养所必需的。很少有报道描述人胸腺衍生（T）细胞系的连续培养，并且当成功时，仅从急性淋巴细胞白血病患者中建立了细胞系4。虽然这些细胞系已显示具有正常人T淋巴细胞的表面标记，但还没有报道表明它们具有对免疫刺激作出反应或分化成抗原特异性淋巴细胞的能力。细胞毒性鼠T细胞仅通过重复的混合淋巴细胞刺激保持连续培养5。与长期的人淋巴细胞系相反，这些细胞仅在用同种异体淋巴细胞刺激时增殖，并最终在培养几周后死亡。Morgan，Ruscetti和Gallo最近报道了一种方法，通过该方法，由植物血凝素刺激的正常人淋巴细胞调节的培养基允许正常T细胞的选择性长期生长6。与前面提到的细胞系相反，这些报道的T细胞培养物的增殖完全依赖于条件培养基提供的外源产生的生长因子的存在。在这份报告中，我们描述了这种方法的适应，它允许长期培养抗原选择的细胞毒性T细胞，在培养4个月以上后继续表现出高水平的同基因肿瘤特异性细胞毒性。
MANY investigators have been successful in the maintenance of long term tissue culture of human bone marrow-derived (B) cells. These cell lines have been established from both normal subjects1and from patients with lymphoproliferative disorders2. In most cases, long term B-cell lines have been shown to harbour the Epstein–Barr virus genome which some investigators feel is required for establishment and maintenance of long-term cultures3. There are fewer reports describing continuous culture of human thymus derived (T) cell lines, and when successful, the lines have only been established from patients with acute lymphocytic leukaemia4. Although these cell lines have been shown to bear surface markers of normal human T lymphocytes, there have been no reports which suggest that they possess the ability to respond to immunologic stimuli or to differentiate into antigen-specific lymphocytes. Cytotoxic murine T cells have been kept in continuous culture only through repetitive mixed-lymphocyte stimulation5. In contrast to long term human lymphocyte lines, these cells proliferated only when stimulated with allogeneic lymphocytes and eventually died after a few weeks in culture. Morgan, Ruscetti and Gallo recently reported a method by which medium conditioned by phytohaemagglutinin-stimulated normal human lymphocytes allowed for the selective long-term growth of normal T cells6. In contrast to the previously mentioned cell lines, the proliferation of these reported T-cell cultures was totally dependent on the presence of an exogenously-produced growth factor supplied by the conditioned medium. In this report we describe an adaptation of this method which allows the long term culture of antigen-selected cytotoxic T cells which continue to demonstrate high levels of syngeneic tumour-specific cytotoxicity after more than 4 months in culture.