Importance of particle size of oligomannose-coated liposomes for induction of Th1 immunity
Importance of particle size of oligomannose-coated liposomes for induction of Th1 immunity
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DOI：
10.1016/j.intimp.2021.108068
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发表时间：
2021-08-17
影响因子：
5.6
通讯作者：
Kuroda, Yasuhiro
中科院分区：
文献类型：
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作者：
Matsuoka, Yuko;Onohara, Emi;Kuroda, Yasuhiro
由二棕榈酰磷脂酰胆碱、胆固醇和Man3-DPPE以1：1：0.1的摩尔比组成、粒径约1000 nm的低聚甘露糖包被脂质体（OML）可诱导脂质体包裹的抗原特异性强Th1免疫。在这项研究中，我们评估了OML颗粒大小对诱导小鼠Th1免疫应答的影响。从用包封具有1000-和800-nm直径的OML的抗原免疫的小鼠获得的脾细胞在体外刺激时分泌显著高水平的IFN-γ。此外，接受这些OML的小鼠血清中抗原特异性IgG2a的滴度显著高于IgG1的滴度，这通常与Th1应答相关。相反，用具有400-和200-nm直径的抗原包封的OML处理未能诱导IFN-γ从脾细胞分泌，尽管这些OML确实引起抗原特异性IgG的升高。此外，血清抗原特异性IgG2a的滴度与接受400 nm OML的小鼠中的IgG1的滴度相同。用直径400 nm的OML处理的居民腹膜单核吞噬细胞（MNP）未能产生这种细胞因子。然而，400 nm的OML确实诱导MNP上MHC II类和共刺激分子的表达增强，类似于600 nm的OML。综上所述，这些结果强烈表明，直径> 600 nm的OML是诱导针对OML包裹的抗原的Th1免疫应答所必需的，尽管直径<400 nm的OML可以激活MNP。
Oligomannose-coated liposomes (OMLs) comprised of dipalmitoylphosphatidylcholine, cholesterol and Man3-DPPE at a molar ratio of 1:1:0.1 and particle diameters of about 1000 nm can induce liposome-encased antigen-specific strong Th1 immunity. In this study, we evaluated the effect of particle sizes of OMLs on induction of Th1 immune responses in mice. Spleen cells obtained from mice immunized with antigen encapsulating OMLs with 1000-and 800-nm diameters secreted remarkably high levels of IFN-gamma upon in vitro stimulation. In addition, sera of mice that received these OMLs had significantly higher titers of antigen-specific IgG2a than those of IgG1, which are commonly associated with Th1 responses. In contrast, treatment with antigen-encapsulating OMLs with 400-and 200-nm diameters failed to induce IFN-gamma secretion from spleen cells, although these OMLs did elicit elevation of antigen-specific IgGs. In addition, the titers of serum antigen-specific IgG2a were the same as those of IgG1 in mice that received 400-nm OMLs. Resident peritoneal mononuclear phagocytes (MNPs) treated with OMLs of diameter 400 nm failed to produce this cytokine. However, 400-nm OMLs did induce enhanced expression of MHC class II and costimulatory molecules on MNPs, similarly to OMLs of 600 nm. Taken together, these results strongly indicate that OMLs of diameter > 600 nm are required to induce Th1 immune responses against OML-encased antigens, although OMLs of diameter < 400 nm can activate MNPs.