Alving C R, Wassef N M
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
AIDS Res Hum Retroviruses. 1994;10 Suppl 2:S91-4.
It is known that liposomes can deliver encapsulated substances, including drugs and antigens, to lysosomes in macrophages. Because of this it has been assumed that although liposomes might be useful for induction of humoral (class II) immunity, they would not be capable of cytoplasmic delivery of antigen for introduction into the class I pathway leading to induction of cytotoxic T lymphocytes (CTLs). However, experiments conducted by numerous laboratories, including our own, have demonstrated the ability to induce CTLs either in vitro with cultured cells incubated with liposome-associated antigen, or in vivo after immunization of mice or monkeys with liposomes containing associated antigen. Using a monoclonal antibody that recognizes repeating sequences of tetrapeptide epitopes derived from the circumsporozoite protein of Plasmodium falciparum, it has been shown by immunogold electron microscopy that liposomal antigenic epitopes can actually spill from endosomes into the cytoplasm of cultured macrophages. On the basis of this observation, a theoretical intracellular pathway is proposed whereby liposomal antigen is processed by macrophages through a cytoplasmic process that results in delivery of antigenic epitopes to the Golgi apparatus and the endoplasmic reticulum. The liposomal antigenic epitopes would then have the opportunity to associate with class I MHC molecules and undergo vesicular transport to the surface of the cells for presentation and induction of CTLs.
众所周知，脂质体能够将包括药物和抗原在内的包封物质递送至巨噬细胞的溶酶体。因此，人们认为尽管脂质体可能有助于诱导体液（II类）免疫，但它们无法将抗原进行胞质递送以引入I类途径从而诱导细胞毒性T淋巴细胞（CTL）。然而，包括我们自己实验室在内的众多实验室所进行的实验表明，用与脂质体相关抗原孵育的培养细胞在体外能够诱导CTL，或者在用含有相关抗原的脂质体免疫小鼠或猴子后在体内也能诱导CTL。使用一种识别源自恶性疟原虫环子孢子蛋白的四肽表位重复序列的单克隆抗体，免疫金电子显微镜显示脂质体抗原表位实际上可以从内体溢出到培养的巨噬细胞的细胞质中。基于这一观察结果，提出了一种理论上的细胞内途径，即脂质体抗原由巨噬细胞通过一个细胞质过程进行加工，该过程导致抗原表位递送至高尔基体和内质网。然后脂质体抗原表位将有机会与I类MHC分子结合，并经历囊泡转运至细胞表面进行呈递并诱导CTL。
