Ju S T, Panka D J, Cui H, Ettinger R, el-Khatib M, Sherr D H, Stanger B Z, Marshak-Rothstein A
Arthritis Center, Boston University School of Medicine, Massachusetts 02118.
Nature. 1995 Feb 2;373(6513):444-8. doi: 10.1038/373444a0.
Receptor crosslinking of T-cell hybridomas induces cell activation followed by apoptosis. This activation-induced cell death requires de novo synthesis of RNA and proteins, but the actual gene products that provide the death signal have not been identified. We show here that receptor crosslinking induces Fas ligand and upregulates Fas, and that the ensuing engagement of Fas by Fas ligand activates the cell-death programme. Cell death, but not activation, can be selectively prevented by a soluble Fas-immunoglobulin fusion protein. Thus, Fas and Fas ligand are the death-gene products, and their interaction accounts for the molecular mechanism of activation-induced T-cell death.
T细胞杂交瘤的受体交联可诱导细胞活化，随后发生凋亡。这种活化诱导的细胞死亡需要RNA和蛋白质的从头合成，但尚未鉴定出提供死亡信号的实际基因产物。我们在此表明，受体交联可诱导Fas配体并上调Fas，并且随后Fas配体与Fas的结合激活细胞死亡程序。可溶性Fas-免疫球蛋白融合蛋白可选择性地阻止细胞死亡而非活化。因此，Fas和Fas配体是死亡基因产物，它们的相互作用解释了活化诱导的T细胞死亡的分子机制。
