Lipid Microbubble-Conjugated Anti-CD3 and Anti-CD28 Antibodies (Microbubble-Based Human T Cell Activator) Offer Superior Long-Term Expansion of Human Naive T Cells In Vitro.
Lipid Microbubble-Conjugated Anti-CD3 and Anti-CD28 Antibodies (Microbubble-Based Human T Cell Activator) Offer Superior Long-Term Expansion of Human Naive T Cells In Vitro.
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DOI：
10.4049/immunohorizons.2000056
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发表时间：
2020-08-07
期刊：
影响因子：
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通讯作者：
Weng NP
中科院分区：
文献类型：
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作者：
Lustig A;Manor T;Shi G;Li J;Wang YT;An Y;Liu YT;Weng NP
用固定化的抗CD3和抗CD28抗体体外刺激人原代T细胞，为研究T细胞的活化和增殖提供了一个系统，也为免疫治疗提供了一条扩增T细胞的途径。以抗CD3和抗CD28单抗偶联的磁珠(D-TCA)已成为体外刺激人原代T细胞的金标准。在这项研究中，我们报道了用抗CD3和抗CD28抗体结合到脂质微泡(基于微泡的人T细胞激活剂[MB-TCA])来刺激原代人类初始T细胞，其扩增效果优于D-TCA。在三个重复刺激周期(每次刺激14d)的56d培养中，我们发现：1)MB-TCA刺激的初始CD4+和CD8+T细胞的扩增效果明显好于D-TCA(20和10倍)，2)MB-TCA和D-TCA刺激的T细胞的初始分裂数相似，但MB-TCA的激活诱导的细胞死亡明显低于D-TCA；(4)通过加入抗肿瘤坏死因子受体抗体(TnFRSF1a)来阻断肿瘤坏死因子-α的作用，可显著促进D-α激活的T细胞的体外扩增。总之，我们证明了MB-TCA在体外能更好地诱导人类初始T细胞的增殖，并且在基础和临床应用中都具有优势，在这些应用中，结果取决于T细胞的数量。《免疫地平线》，2020，4：475-484。
Stimulation of human primary T cells with immobilized anti-CD3 and anti-CD28 Abs in vitro provide a system to study T cell activation and proliferation and an avenue for expanding T cells for immunotherapy. Magnetic beads conjugated with anti-CD3 and anti-CD28 Abs (Dynabeads Human T-Activator [D-TCA]) have been a golden standard for stimulating human primary T cells in vitro. In this study, we report that an application using anti-CD3 and anti-CD28 Abs conjugated on lipid microbubbles (microbubble-based human T cell activator [MB-TCA]) to stimulate primary human naive T cells resulted in expansion superior to D-TCA. In 56-d cultures with three repeated stimulation cycles (14 d per stimulation), we found that 1) MB-TCA induced significantly better expansion (20- and 10-fold increase) of naive CD4+ and CD8+ T cells than did D-TCA; 2) MB-TCA–and D-TCA–stimulated T cells had a similar number of initial cell divisions, but MB-TCA had significantly lower activation-induced cell death than D-TCA; 3) MB-TCA–stimulated T cells produced less TNF-a than did D-TCA; and 4) blocking TNF-a action via adding an Ab against TNF-αR (TNFRSF1A) significantly improved expansion of T cells activated by D-TCA in vitro. Together, we demonstrated that the MB-TCA induces a better expansion of human naive T cells in vitro and offers advantages in both basic and clinical applications in which the outcome depends on the number of T cells. ImmunoHorizons, 2020, 4: 475–484.