Accelerated apoptosis in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus type-1 infected patients and in CD4 cross-linked PBMCs from normal individuals.
This study investigates apoptosis as a mechanism for CD4+ T-cell depletion in human immunodeficiency virus type-1 (HIV-1) infection. Although several recent studies have shown that T cells of HIV-infected individuals show enhanced susceptibility to cell death by apoptosis, the mechanisms responsible for apoptosis are largely unknown. By using a flow cytometric technique and by morphology, we have quantitated the percentage of cells undergoing apoptosis in peripheral blood mononuclear cells (PBMCs) from HIV-seronegative donors and from HIV-infected asymptomatic patients. The PBMCs were cultured without any stimulus or with staphylococcus enterotoxin B, anti-T-cell receptor (TCR) alpha beta monoclonal antibody WT-31, or phytohemagglutinin for periods up to 6 days. In addition, we sought to determine whether cross-linking of CD4 followed by various modes of TCR stimulation in vitro could induce apoptosis in normal PBMCs. Here we show that (1) patient PMBCs undergo marked spontaneous apoptosis; (2) stimulation of T cells of patients as well as normal donors results in increased apoptosis; and (3) cross-linking of CD4 molecules is sufficient to induce apoptosis in CD4+ T cells if cross-linking is performed in unfractioned PBMCs, but not if CD4 molecules are cross-linked in purified T-cell preparations. These observations strongly suggest that accelerated cell death through apoptosis plays an important role in the pathogenesis of HIV-1 infection. At the same time, our observations implicate cross-linking of CD4 in vivo as a major contributor to this mechanism of accelerated cell death in HIV infection.
Oyaizu
N
N
Department of Pediatrics, North Shore University Hospital, Cornell University Medical College, Manhasset, NY 11030.
McCloskey
T W
TW
Coronesi
M
M
Chirmule
N
N
Kalyanaraman
V S
VS
Pahwa
S
S
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D017209:Apoptosis; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000502:physiology
D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell