Differential expression of bcl-2 and susceptibility to programmed cell death in lymphocytes of HIV-1-infected individuals

• Published in: Clinical immunology and immunopathology 1998-06, Vol.87 (3), p.230-239
• Main Authors: DOBMEYER, T. S, KLEIN, S. A, DOBMEYER, J. M, RAFFEL, B, FINDHAMMER, S, HOELZER, D, HELM, E. B, ROSSOL, R, KABELITZ, D
• Format: Article
• Language: English
• Subjects: Adult; AIDS/HIV; Antibodies, Monoclonal; Apoptosis - physiology; Biological and medical sciences; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Down-Regulation; Flow Cytometry; HIV Infections - blood; HIV Infections - pathology; HIV-1; Human viral diseases; Humans; Infectious diseases; Lymphocyte Activation; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes - pathology; Male; Medical sciences; Middle Aged; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - blood; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0090-1229; 1090-2341
• DOI: 10.1006/clin.1997.4465

The bcl-2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death. There is now increasing evidence that regulation of bcl-2 expression is a determinant of life or death in normal lymphocytes. In this study, we examined bcl-2 expression in lymphocytes from human immunodeficiency virus type 1 (HIV-1)-infected and healthy subjects by flow cytometry. bcl-2 expression 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/microliter expressed significantly less bcl-2 than healthy controls. In contrast, bcl-2 expression in CD8+ lymphocytes of these patients was significantly enhanced. No significant alteration of bcl-2 expression was found when lymphocytes of healthy individuals were polyclonally activated in the presence of various regulatory cytokines. Cells undergoing apoptosis showed significantly lower bcl-2 expression 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 different bcl-2 expression in CD4+ and CD8+ lymphocytes of HIV-1-infected individuals with less than 200 CD4+ cells/microliter, no difference could be observed concerning their susceptibility to undergo apoptosis. Therefore, we conclude that sensitivity or resistance to in vitro induction of apoptosis does not directly correlate with bcl-2 expression.