Differential Expression ofbcl-2and Susceptibility to Programmed Cell Death in Lymphocytes of HIV-1-Infected Individuals

Abstract

Thebcl-2protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death. There is now increasing evidence that regulation ofbcl-2expression is a determinant of life or death in normal lymphocytes. In this study, we examinedbcl-2expression in lymphocytes from human immunodeficiency virus type 1 (HIV-1)-infected and healthy subjects by flow cytometry.bcl-2expression was detected in more than 97% of peripheral blood lymphocytes in both healthy and HIV-infected individuals. It was consistently observed that CD4+ lymphocytes from HIV-1-infected individuals with less than 200 CD4+ cells/μl expressed significantly lessbcl-2than healthy controls. In contrast,bcl-2expression in CD8+ lymphocytes of these patients was significantly enhanced. No significant alteration ofbcl-2expression was found when lymphocytes of healthy individuals were polyclonally activated in the presence of various regulatory cytokines. Cells undergoing apoptosis showed significantly lowerbcl-2expression than viable cells. Staining of apoptotic cells revealed that lymphocytes from HIV-1-infected subjects were characterized by an increased susceptibility to programmed cell death which was not restricted to a particular lymphocyte subset. Despite significantly differentbcl-2expression in CD4+ and CD8+ lymphocytes of HIV-1-infected individuals with less than 200 CD4+ cells/μl, no difference could be observed concerning their susceptibility to undergo apoptosis. Therefore, we conclude that sensitivity or resistance toin vitroinduction of apoptosis does not directly correlate withbcl-2expression.