Differential expression of bcl-2 and susceptibility to programmed cell death in lymphocytes of HIV-1-infected individuals.
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.
Dobmeyer
T S
TS
Department of Medicine III, University of Frankfurt, Germany.
Klein
S A
SA
Dobmeyer
J M
JM
Raffel
B
B
Findhammer
S
S
Hoelzer
D
D
Helm
E B
EB
Rossol
R
R
Kabelitz
D
D
D000328:Adult; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000502:physiology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000097:blood*
D000911:Antibodies, Monoclonal; D019253:Proto-Oncogene Proteins c-bcl-2