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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
N Oyaizu, TW McCloskey, M Coronesi, N Chirmule, VS Kalyanaraman and S Pahwa
Department of Pediatrics, North Shore University Hospital, Cornell
University Medical College, Manhasset, NY 11030.
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.
Volume 82,
Issue 11,
pp. 3392-3400,
12/01/1993
Copyright © 1993 by The American Society of Hematology
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