Fas-mediated apoptosis of CD4+ and CD8+ T cells from human immunodeficiency virus-infected persons: differential in vitro preventive effect of cytokines and protease antagonists.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Fas-mediated apoptosis of CD4+ and CD8+ T cells from human immunodeficiency virus-infected persons: differential in vitro preventive effect of cytokines and protease antagonists.

Blood. 1996 Jun 15;87(12):4959-66. Unique Identifier : AIDSLINE MED/96247497
Estaquier J; Tanaka M; Suda T; Nagata S; Golstein P; Ameisen JC; Inserm U415, Lille, France.

Abstract: Human immunodeficiency syndrome (HIV) infection leads to a progressive loss of T-cell-mediated immunity associated with T-cell apoptosis. We report here that CD4+ and CD8+ T cells from HIV-1-infected persons are sensitive to Fas (CD95/APO-1)-mediated death induced either by an agonistic anti-Fas antibody or by the physiologic soluble Fas ligand, although showing no sensitivity to tumor necrosis factor alpha-induced death. CD4+ and CD8+ T-cell apoptosis induced by Fas ligation was enhanced by inhibitors of protein synthesis and was prevented either by a soluble Fas receptor decoy or an antagonistic anti-Fas antibody. Fas-mediated apoptosis could also be prevented in a CD4+ or CD8+ T-cell-type manner (1) by several protease antagonists, suggesting the involvement of the interleukin-1beta (IL-1beta)-converting enzyme (ICE)-related cysteine protease in CD4+ T-cell death and of both a CPP32-related cysteine protease and a calpain protease in CD8+ T-cell death; and (2) by three cytokines, IL-2, IL-12, and IL-10, that exerted their effects through a mechanism that required de novo protein synthesis. Finally, T-cell receptor (TCR)-induced apoptosis of CD4+ T cells from HIV-infected persons involved a Fas-mediated death process, whereas TCR stimulation of CD8+ T cells led to a different Fas-independent death process. These findings suggest that Fas-mediated T-cell death is involved in acquired immunodeficiency syndrome (AIDS) pathogenesis and that modulation of Fas-mediated signaling may represent a target for new therapeutic strategies aimed at the prevention of CD4+ T-cell death in AIDS.

Keywords: Animal Antibodies, Monoclonal/PHARMACOLOGY Antigens, CD95/DRUG EFFECTS/*PHYSIOLOGY *Apoptosis/DRUG EFFECTS Base Sequence Calpain/PHYSIOLOGY Cysteine Proteinases/PHYSIOLOGY CD4-Positive T-Lymphocytes/DRUG EFFECTS/*PATHOLOGY CD8-Positive T-Lymphocytes/DRUG EFFECTS/*PATHOLOGY Human HIV Infections/IMMUNOLOGY/*PATHOLOGY HIV-1 Membrane Glycoproteins/PHARMACOLOGY Mice Molecular Sequence Data Protease Inhibitors/PHARMACOLOGY Protein Synthesis Inhibitors/PHARMACOLOGY Receptors, Antigen, T-Cell/PHYSIOLOGY Recombinant Fusion Proteins/PHARMACOLOGY Signal Transduction Support, Non-U.S. Gov't JOURNAL ARTICLE
961030
M96A1414

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