PMID: 9002958Jan 15, 1997Paper

A cysteine protease inhibitor prevents activation-induced T-cell apoptosis and death of peripheral blood cells from human immunodeficiency virus-infected individuals by inhibiting upregulation of Fas ligand.

Blood
Y YangJ D Ashwell

Abstract

Activation of T-cell hybridomas, preactivated normal T cells, and peripheral blood lymphocytes (PBL) from human immunodeficiency virus (HIV)-infected individuals results in apoptosis. In the first two cases, apoptosis is caused by the upregulation of Fas ligand (FasL) and its subsequent interaction with Fas; the mechanism for the spontaneous and activation-induced death of lymph node cells and PBL from HIV+ blood is not known. A number of protease inhibitors have been shown to prevent T-cell apoptosis under all of these circumstances, but the mechanism of action has not been determined. Here we show that the cysteine protease inhibitor E64d prevent activation-induced T hybridoma cell death by inhibiting the upregulation of FasL. Quantitative polymerase chain reaction (PCR) demonstrated that mRNA for FasL is expressed at low levels in fresh PBL from HIV-infected blood, but increases in cultured PBL from both uninfected and HIV-infected donors. The ex vivo apoptosis of PBL from HIV+ donors was prevented by adding the soluble extracellular domain of Fas, demonstrating a requisite role for Fas/ FasL interactions in this form of cell death. Furthermore, while having no effect on the death of PBL from HIV-infected blood stimulated di...Continue Reading

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis