Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes.
Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes.
复制标题
细胞毒性T淋巴细胞颗粒是分泌的溶酶体，含有穿孔蛋白和颗粒酶。
DOI：
10.1084/jem.173.5.1099
复制
发表时间：
1991-05-01
期刊：
影响因子：
--
通讯作者：
Geuze HJ
中科院分区：
文献类型：
--
作者：
Peters PJ;Borst J;Oorschot V;Fukuda M;Krähenbühl O;Tschopp J;Slot JW;Geuze HJ
细胞毒性T淋巴细胞（CTL）含有在与靶细胞（TC）特异性相互作用期间胞吐的颗粒。在这个过程中，颗粒内容物，包括致死蛋白穿孔素，以及颗粒酶，丝氨酸酯酶家族，被传递到TC。关于这些蛋白质向颗粒的路由及其在颗粒内的精确定位的信息对于解决颗粒介导的TC杀伤的机制是至关重要的。在这项研究中，穿孔素，颗粒酶，和已知的内体和溶酶体标记蛋白的亚细胞定位确定在人类和小鼠CTL，免疫金标记的冷冻切片，然后通过电子显微镜。穿孔蛋白和颗粒酶可以在粗面内质网、高尔基复合体、反式高尔基网和所有细胞毒性颗粒中检测到。在颗粒内，它们具有相似的分布，不仅位于所谓的致密核心中，而且位于含有小内囊泡的区域上。这一发现意味着穿孔素和颗粒酶可以以膜包被和/或膜结合的形式释放到CTL-TC相互作用后形成的细胞间隙中。根据目前的证据，不能排除这些分子以可溶形式的额外释放。溶酶体膜糖蛋白lamp-1、lamp-2和CD 63大量存在于颗粒界定外膜上，其在致命命中递送期间并入CTL质膜中。与此相反，阳离子依赖性甘露糖6-磷酸受体，已知存在于内体和溶酶体缺席，被发现只在少数的颗粒。结合我们以前的发现，即颗粒是酸性的，并连接到内吞途径，这些观察定义CTL颗粒作为分泌溶酶体。
Cytotoxic T lymphocytes (CTL) contain granules that are exocytosed during specific interaction with target cells (TC). In this process, the granule contents, including the lethal protein perforin, as well as granzymes, a family of serine esterases, are delivered to the TC. Information regarding the routing of these proteins towards the granule and their exact localization within the granule is of primary importance to resolve the mechanism of granule-mediated TC killing. In this study, the subcellular localization of perforin, granzymes, and known endosomal and lysosomal marker proteins was determined in human and murine CTL, by immunogold labeling of ultrathin cryosections followed by electron microscopy. Perforin and granzymes can be detected in rough endoplasmic reticulum, Golgi complex, trans-Golgi reticulum, and in all cytotoxic granules. Within the granules, they have a similar distribution and are localized not only in the so-called dense core but also over the region containing small internal vesicles. This finding implies that perforin and granzymes can be released in membrane- enveloped and/or -associated form into the intercellular cleft formed upon CTL-TC interaction. On the basis of the present evidence, additional release of these molecules in soluble form cannot be excluded. The lysosomal membrane glycoproteins lamp-1, lamp-2, and CD63, are abundantly present on the granule-delimiting outer membrane, which becomes incorporated into the CTL plasma membrane during lethal hit delivery. In contrast, the cation-dependent mannose 6-phosphate receptor, known to be present in endosomes and absent from lysosomes, is found only in a minority of the granules. Together with our previous findings that the granules are acidic and connected to the endocytic pathway, these observations define CTL granules as secretory lysosomes.