Ogasawara J, Suda T, Nagata S
Osaka Bioscience Institute, Japan.
J Exp Med. 1995 Feb 1;181(2):485-91. doi: 10.1084/jem.181.2.485.
Fas is a cell surface protein that mediates apoptosis. A mouse mutant, lpr (lymphoproliferation), has a mutation in the Fas gene. In this report, we studied the expression and function of Fas in various subpopulations of mouse thymocytes. Abundant expression of Fas was detected on CD4+CD8+ double positive as well as CD4+ or CD8+ single positive thymocytes in wild-type mice. Little or low levels of Fas were expressed in CD4-CD8- double negative thymocytes except for the CD4-CD8-CD3+ phenotype, which expresses Fas as abundantly as double positive or single positive subsets. On the other hand, no Fas expression was detected in any population of thymocytes from lpr mice. When the wild-type thymocytes were treated with the agonistic anti-Fas antibody, double positive cells from the wild-type mice were selectively killed by apoptosis, whereas, the single positive cells were resistant to its cytolytic activity despite their abundant expression of Fas. Unlike the apoptosis of thymocytes induced by glucocorticoid or T cell activator, the Fas-induced apoptosis of thymocytes was enhanced by metabolic inhibitors such as cycloheximide. Furthermore, intraperitoneal administration of the anti-Fas antibody into mice caused rapid apoptosis of thymocytes in vivo.
Fas是一种介导细胞凋亡的细胞表面蛋白。一种小鼠突变体lpr（淋巴细胞增殖），其Fas基因存在突变。在本报告中，我们研究了Fas在小鼠胸腺细胞各亚群中的表达和功能。在野生型小鼠的CD4+CD8+双阳性以及CD4+或CD8+单阳性胸腺细胞上检测到Fas的丰富表达。除了CD4-CD8-CD3+表型外，CD4-CD8-双阴性胸腺细胞中Fas表达很少或水平较低，而CD4-CD8-CD3+表型表达Fas的水平与双阳性或单阳性亚群一样丰富。另一方面，在lpr小鼠的任何胸腺细胞群体中均未检测到Fas表达。当野生型胸腺细胞用抗Fas激动性抗体处理时，野生型小鼠的双阳性细胞通过凋亡被选择性杀死，而单阳性细胞尽管大量表达Fas，但对其细胞溶解活性具有抗性。与糖皮质激素或T细胞激活剂诱导的胸腺细胞凋亡不同，Fas诱导的胸腺细胞凋亡可被代谢抑制剂如环己酰亚胺增强。此外，向小鼠腹腔注射抗Fas抗体可在体内导致胸腺细胞快速凋亡。
