Arginine-based cationic liposomes accelerate T cell activation and differentiation in vitro
Arginine-based cationic liposomes accelerate T cell activation and differentiation in vitro
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DOI：
10.1016/j.ijpharm.2022.121917
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发表时间：
2022-07-25
影响因子：
5.8
通讯作者：
Takeoka, Shinji
中科院分区：
文献类型：
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作者：
Li, Tianshu;Tolksdorf, Felix;Takeoka, Shinji
阳离子脂质体是一种多功能的脂质纳米载体，可改善药物有效载荷的药理学性质。最近的优势包括应用其内在的免疫刺激作用来增强免疫激活。在此，我们首次报道了阳离子脂质在体外促进T细胞活化和分化的结构效应。由单一类型的脂质Arg-C3-Clu 2C 14或Arg-C5-Clu 2C 14制备了两种类型的阳离子脂质体R3 C14和R5 C14，所述脂质体具有精氨酸头基和双十四烷基尾基，但其间的间隔基的碳数不同。用50 μ M的每种类型的脂质体预处理鼠CD 8或CD 4 T细胞2小时，然后用抗CD 3/CD 28抗体刺激24小时。与脂质体未处理的T细胞相比，R5 C14预处理诱导了稳健的T细胞活化（IL-2，CD 25+）和分化为效应细胞（CD 44高，CD 62低），而R3 C14没有显示出相当的效果。此外，在Jurkat-Lucia NFAT细胞（InvivoGen）中检测到活化T细胞核因子（NFAT）的弱活化，表明脂质体效应的潜在信号传导途径。虽然R5 C14脂质体在没有随后的CD 3/CD 28刺激的情况下不能激活T细胞，但该研究暗示了一些阳离子佐剂在引发T细胞以增强其对抗原的反应性中的隐性效应。
Cationic liposomes are versatile lipid nanocarriers to improve the pharmacological properties of drug payloads. Recent advantages include the application of their intrinsic immunostimulatory effects to enhance immune activation. Herein, we report for the first time the structural effect of cationic lipids in promoting T cell activation and differentiation in vitro. Two types of cationic liposomes R3C14 and R5C14 were prepared from single type of lipids Arg-C3-Clu2C14 or Arg-C5-Clu2C14, which bear arginine head group and ditetradecyl tails but vary in the carbon number of the spacer in between. Murine CD8 or CD4 T cells were pretreated with 50 mu M of each type of liposomes for 2 h, followed by stimulation with anti-CD3/CD28 antibodies for 24 h. In comparison to liposome-untreated T cells, R5C14-pretreatment induced a robust T cell activation (IL-2, CD25+) and differentiation into effector cells (CD44high, CD62Llow), whereas R3C14 did not show comparable effect. Furthermore, a weak activation of nuclear factor of activated T cells (NFAT) was detected in Jurkat-Lucia NFAT cells (InvivoGen), suggesting a potential signaling pathway for the liposomal effect. Although R5C14 liposomes did not activate T cells without subsequent CD3/CD28 stimulation, this study implied a recessive effect of some cationic adjuvant in priming T cells to enhance their responsiveness to antigens.