Propagation of mouse and human T cells with defined antigen specificity and function.

Propagation of mouse and human T cells with defined antigen specificity and function.
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具有明确抗原特异性和功能的小鼠和人类 T 细胞的增殖。

DOI:
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发表时间:
1994
期刊:
Ciba Foundation symposium
影响因子:
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通讯作者:
S. Rosenberg
S. Rosenberg
中科院分区:
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文献类型:
--
作者:
P. Cohen;D. Fowler;H. Kim;R. White;B. Czerniecki;C. Carter;R. Gress;S. Rosenberg

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在培养物中维持完全功能性CD 4 + T细胞的困难在历史上限制了它们在肿瘤排斥反应中的作用的研究以及其他临床应用。随着当前抗肿瘤CD 8 + T细胞过继疗法的治疗价值变得更好地定义,存在确定用于培养抗肿瘤CD 4 + T细胞的最佳条件的强大动力。我们的目标是促进广泛的多克隆,抗原特异性的CD 4 + T细胞反应的Th 1或Th 2字符用于抗肿瘤治疗或同种异体移植物的促进,分别。在鼠和人培养物中存在类似的障碍:(1)在甚至短暂的培养期间,CD 4 + T细胞对II类阳性抗原呈递细胞产生高的“背景”反应性;(2)如细胞因子分泌和短期增殖测定所证明的,抗原特异性的维持不足以确保大量的数值扩增;(3)Th 1型CD 4 + T细胞在再刺激时往往失去其抗原特异性分泌白细胞介素2的潜力(尽管仍能被12-O-十四酰基佛波醇13-乙酸酯/离子霉素诱导);(4)在延长的培养过程中,选择压力有利于识别人工抗原如培养基蛋白的CD 4+亚群;(5)即使在最佳培养条件下,培养的CD 4 + T细胞在体内的功能也可能与未培养的CD 4 + T细胞不同。我们已经设计了各种策略来克服这些障碍,通过使用选定的细胞因子,抗原呈递细胞和及时的文化演习。
Difficulties maintaining fully functional CD4+ T cells in culture have historically limited the study of their role in tumour rejection as well as other clinical applications. As the therapeutic value of current antitumour CD8+ T cell adoptive therapy becomes better defined, a strong impetus exists to determine optimal conditions for culturing antitumour CD4+ T cells. Our goal is to promote broadly polyclonal, antigen-specific CD4+ T cell responses of either Th1 or Th2 character for use in antitumour therapy or allograft facilitation, respectively. Similar obstacles exist in murine and human cultures: (1) during even brief periods of culture CD4+ T cells develop high 'background' reactivity to class II-positive antigen-presenting cells; (2) maintenance of antigen specificity as evidenced by cytokine secretion and short-term proliferation assays is insufficient to ensure bulk numerical expansion; (3) Th1-type CD4+ T cells often lose their potential for antigen-specific secretion of interleukin 2 on re-stimulation (though remain inducible by 12-O-tetradecanoylphorbol 13-acetate/ionomycin); (4) during prolonged culture selection pressure favours CD4+ subpopulations that recognize artifactual antigens such as culture medium proteins; (5) even with optimal culture conditions, cultured CD4+ T cells may function differently in vivo to uncultured CD4+ T cells. We have devised various strategies to surmount these obstacles by use of selected cytokines, antigen-presenting cells and timely culture manoeuvres.
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