Garnier F, Forquet F, Bertolino P, Gerlier D
INSERM U218, Centre Léon Bérard, Lyon, France.
Vaccine. 1991 May;9(5):340-5. doi: 10.1016/0264-410x(91)90061-a.
Artificial phospholipid bilayer vesicles were tested for their capacity to enhance the priming and the restimulation of mouse T cells against the haemagglutinin (H) glycoprotein of the measles virus in vivo and in vitro. H glycoprotein was purified and incorporated into liposomes made of cholesterol, dicetylphosphate and dilauroylphosphatidylcholine (DLPC) or distearoylphosphatidylcholine (DSPC). H in DLPC or DSPC-liposomes was found to be a potent in vivo stimulator of lymph node T cells harvested from mice immunized with measles virus, whereas H glycoprotein in free form did not elicit any proliferative T cell response. When used to immunize naive mice, only H in DSPC-liposomes was able to prime T cells as evidenced by the capacity of lymph node cells to proliferate in the presence of H in liposomes or measles virus as secondary stimulating agents in vitro. H-specific T cell clones derived from animals immunized with H in DSPC-liposomes were able to recognize H glycoprotein both in free form and incorporated into liposomes in the presence of naive spleen cells as APC. However, compared with the liposome forms, 20-fold more H protein in free form was required to elicit a T cell clone response at a similar level. This liposome immune enhancing effect on the T cell clone recognition of H glycoprotein was also observed when peritoneal exudate cells were used as APC. These data demonstrate that the insertion of a membrane-derived antigen into artificial membranes may be a prerequisite for the priming and stimulation of specific T cells both in vivo and in vitro. In addition, the nature of the phospholipid used to build the liposomes appears to be a critical parameter.
对人工磷脂双层囊泡增强小鼠T细胞针对麻疹病毒血凝素(H)糖蛋白的初次免疫和再次刺激的能力进行了体内和体外测试。H糖蛋白被纯化并掺入由胆固醇、磷酸二鲸蜡酯和二月桂酰磷脂酰胆碱(DLPC)或二硬脂酰磷脂酰胆碱(DSPC)制成的脂质体中。发现DLPC或DSPC脂质体中的H是从用麻疹病毒免疫的小鼠收获的淋巴结T细胞的有效体内刺激剂,而游离形式的H糖蛋白不会引发任何增殖性T细胞反应。当用于免疫未免疫的小鼠时,只有DSPC脂质体中的H能够使T细胞致敏,这可通过淋巴结细胞在脂质体中的H或麻疹病毒作为体外二次刺激剂存在下增殖的能力来证明。源自用DSPC脂质体中的H免疫的动物的H特异性T细胞克隆能够在存在作为抗原呈递细胞的未免疫脾细胞的情况下识别游离形式和掺入脂质体中的H糖蛋白。然而,与脂质体形式相比,需要20倍以上的游离形式的H蛋白才能引发相似水平的T细胞克隆反应。当使用腹腔渗出细胞作为抗原呈递细胞时,也观察到了这种脂质体对T细胞克隆识别H糖蛋白的免疫增强作用。这些数据表明,将膜衍生抗原插入人工膜中可能是体内和体外引发和刺激特异性T细胞的先决条件。此外,用于构建脂质体的磷脂的性质似乎是一个关键参数。