Efficacy of IL-2-versus IL-15-stimulated CD8 T cells in adoptive immunotherapy
Efficacy of IL-2-versus IL-15-stimulated CD8 T cells in adoptive immunotherapy
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DOI：
10.1002/eji.200838426
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发表时间：
2008-10-01
影响因子：
5.4
通讯作者：
Pircher, Hanspeter
中科院分区：
文献类型：
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作者：
Mueller, Katja;Schweier, Oliver;Pircher, Hanspeter
我们测定了体外扩增的P14TCR转基因CD8T细胞对小鼠肿瘤细胞的清除和对病毒感染的保护作用。与以前的研究相反，采用了一种过继转移模型，不需要淋巴清除、疫苗接种或细胞因子治疗。在含有IL-2的培养液中培养7天的抗原激活的P14 T细胞(P14(IL-2))在体外显示出强大的效应细胞功能，但对黑色素瘤生长或病毒感染没有保护作用。相反，在IL-15(P14(IL-15))中培养的P14 T细胞虽然在体外只表现出中等的效应功能，但在体内是高度有效的。治疗效果与移植T细胞在受者体内的存活有关：P14(IL-2)细胞迅速消失，而P14(IL-15)细胞持续时间较长。降低培养上清液中IL-2的浓度可提高体内存活率和疗效，但也会降低细胞产量。最后，我们可以将单克隆性P14T细胞的研究结果扩展到多克隆性CD8T细胞。因此，在IL-15中体外扩增抗原特异的CD8 T细胞可以在不诱导终末分化的效应细胞的情况下产生大量的T细胞，而这在本文研究的转移模型中是不利的。
We deter-mined the efficacy of in vitro expanded P14 TCR transgenic CD8 T cells to mediate tumor cell elimination and to protect against viral infection in mice. Contrary to previous studies, an adoptive transfer model without lymphodepletion, vaccination or cytokine treatment was used. Antigen-activated P14 T cells cultured in IL-2-containing medium for 7 days (P14(IL-2)) exhibited potent effector cell functions in vitro but did not confer protection against melanoma growth or viral infection. In contrast, P14 T cells cultured in IL-15 (P14(IL-15)) were highly effective in vivo although they displayed only moderate effector functions in vitro. Therapeutic efficacy correlated with the survival of the transferred T cells in the recipients: P14(IL-2) cells disappeared rapidly whereas P14(IL-15) cells persisted for prolonged time. Decreasing the IL-2 concentration in the culture media improved in vivo survival and efficacy but also lowered the cell yield of the cultures. Finally, we could extend the findings with monoclonal P14 T cells to polyclonal CD8 T cells. Thus, in vitro expansion of antigen-specific CD8 T cells in IL-15 allowed the generation of substantial numbers of T cells without inducing terminally differentiated effector cells that turned out to be unfavorable in the transfer model examined here.