Chu J L, Ramos P, Rosendorff A, Nikolić-Zugić J, Lacy E, Matsuzawa A, Elkon K B
Specialized Center of Research in Systemic Lupus Erythematosus, Hospital for Special Surgery-Cornell University Medical Center, New York 10021.
J Exp Med. 1995 Jan 1;181(1):393-8. doi: 10.1084/jem.181.1.393.
Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of T cells with an unusual double negative (DN) (CD4-CD8-) phenotype. Previous studies have shown that these abnormal cells are capable of inducing redirected lysis of certain Fc receptor-positive target cells. Since the Fas ligand (FasL) has recently been shown to be partly responsible for T cell-mediated cytotoxicity, lymph node cells from lpr and gld mice were examined for the expression of FasL mRNA. Northern blot analysis revealed that lymph node cells obtained from lpr and gld mice had a striking increase in the level of expression of FasL mRNA predominantly due to expression in the DN T cells. Furthermore, lpr, but not gld lymph node cells killed the B cell line, A20, in a Fas-dependent manner. These findings indicate that Fas mutations result in a massive up-regulation of FasL which, most likely, results from repetitive exposure to (self) antigen. This phenomenon could explain the lpr-induced wasting syndrome observed when lpr bone marrow-derived cells are adoptively transferred to wild-type recipients.
Fas缺陷的lpr和gld小鼠会因具有异常双阴性（DN）（CD4-CD8-）表型的T细胞积累而出现淋巴结病。先前的研究表明，这些异常细胞能够诱导某些Fc受体阳性靶细胞的重定向裂解。由于最近已证明Fas配体（FasL）部分负责T细胞介导的细胞毒性，因此检测了lpr和gld小鼠的淋巴结细胞中FasL mRNA的表达。Northern印迹分析显示，从lpr和gld小鼠获得的淋巴结细胞中FasL mRNA的表达水平显著增加，这主要是由于DN T细胞中的表达所致。此外，lpr淋巴结细胞而非gld淋巴结细胞以Fas依赖的方式杀死B细胞系A20。这些发现表明，Fas突变导致FasL大量上调，这很可能是由于反复接触（自身）抗原所致。这种现象可以解释当将lpr骨髓来源的细胞过继转移到野生型受体时观察到的lpr诱导的消瘦综合征。
