Long-term growth of lymphokine-activated killer (LAK) cells: role of anti-CD3, beta-IL 1, interferon-gamma and -beta.
Long-term growth of lymphokine-activated killer (LAK) cells: role of anti-CD3, beta-IL 1, interferon-gamma and -beta.
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DOI：
10.4049/jimmunol.138.8.2728
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发表时间：
1987-04
影响因子：
4.4
通讯作者：
A. Ochoa;G. Gromo;B. Alter;P. Sondel;F. Bach
中科院分区：
文献类型：
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作者：
A. Ochoa;G. Gromo;B. Alter;P. Sondel;F. Bach
在常规组织培养中，在含白细胞介素2（IL 2）的培养基中培养的外周血淋巴细胞（PBL）具有裂解新鲜肿瘤细胞的能力;此类细胞被称为淋巴因子激活的杀伤（LAK）细胞。LAK活性在培养第5天达到峰值，此后迅速下降。我们研究了培养条件和信号，允许长期培养和扩增具有LAK活性的细胞。通过以相对低的密度培养细胞并定期补充培养基和重组IL 2（r-IL 2），与短期培养物相比，LAK功能显著更高，并且在细胞数量经历平均100倍扩增的同时保持存在至少21天。通过用抗CD 3（OKT 3）单克隆抗体和r-IL 2激活这些培养物，在维持相当水平的LAK活性的情况下获得细胞数量的约1000倍扩增。外源性添加β白细胞介素1（β-IL 1）、干扰素-β（IFN-β）或干扰素-γ（IFN-γ）可增强抗-CD 3加r-IL 2扩增的细胞群的裂解活性。这些方法可以使个体供体体外产生比现在用3至5天体外培养系统获得的数量大得多的用于过继免疫治疗的LAK细胞。
Peripheral blood lymphocytes (PBL) cultured in interleukin 2 (IL 2)-containing medium in conventional tissue culture develop the ability to lyse fresh tumor cells; such cells are referred to as lymphokine-activated killer (LAK) cells. LAK activity peaks by day 5 of culture and declines rapidly thereafter. We studied culture conditions and signals that allow for long-term culture and expansion of cells with LAK activity. By culturing cells at relatively low densities and regularly replenishing medium and recombinant IL 2 (r-IL 2), LAK function is significantly higher as compared with short-term cultures, and remains present for at least 21 days while cell numbers undergo an average 100-fold expansion. By activating these cultures with anti-CD3 (OKT3) monoclonal antibody and r-IL 2, an approximately 1000-fold expansion in the cell number is obtained with maintenance of comparable levels of LAK activity. The exogenous addition of beta interleukin 1 (beta-IL 1), interferon-beta (IFN-beta) or interferon-gamma (IFN-gamma) can augment the lytic activity of cell populations expanded by anti-CD3 plus r-IL 2. These approaches may enable the in vitro generation from individual donors of much greater numbers of LAK cells for adoptive immunotherapy than can now be obtained with the 3 to 5 day in vitro culture systems.