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In vitro exposure to human immunodeficiency virus type 1 induces apoptotic
cell death of the factor-dependent TF-1 hematopoietic cell line
G Zauli, M Vitale, MC Re, G Furlini, L Zamai, E Falcieri, D Gibellini, G Visani, BR Davis and S Capitani
Institute of Human Anatomy, University of Ferrara, Italy.
In this study, we evaluated the effect of a short-term exposure (2 hours)
to two different lymphocytotropic strains of human immunodeficiency virus
type 1 (HIV-1; HIVIIIB and ICR-3) on the survival of a factor-dependent
CD34+ hematopoietic progenitor cell line (TF-1). At flow cytometry
analysis, a significant (P < .05) increase in the frequency of apoptotic
cell death was observed in HIV-1-treated TF- 1 cells, supplemented with low
doses of either interleukin-3 (IL-3; 0.02 to 1 ng/mL) or
granulocyte-macrophage colony-stimulating factor (GM-CSF; 0.02 to 0.2
ng/mL) with respect to mock-treated cells. On the other hand, higher doses
of both cytokines or combinations of suboptimal concentrations of IL-3 plus
GM-CSF (eg, 0.2, plus 0.2 ng/mL) completely reversed the HIV-1-induced
increase of apoptosis. Remarkably, no signs of productive or latent virus
replication were ever observed in HIV-1-treated TF-1 cells up to 16 days of
liquid culture. In parallel experiments, the in vitro exposure to HIVIIIB
induced a significant and progressive increase of apoptotic death in
purified bone marrow CD34+ cells, seeded in liquid cultures in the presence
of 1 ng/mL IL-3. The HIV-1-induced apoptosis of TF-1 cells was likely
triggered by the simple interaction of HIV-1 envelope glycoprotein gp120
with CD4 receptor, which was expressed at a low level on the surface of
TF-1 cells. In fact, treatment of TF-1 cells with recombinant gp120 plus a
polyclonal anti-gp120 antibody or with anti-CD4 monoclonal antibody plus
rabbit antimouse IgG significantly increased the percentage of apoptotic
death. These data suggest that HIV-1, and perhaps also free gp120 in the
presence of anti-gp120 antibody; could play a direct role in the
pathogenesis of peripheral blood cytopenias in acquired immunodeficiency
syndrome patients by inducing apoptotic death of hematopoietic progenitor
cells without the need of a direct infection.
Volume 83,
Issue 1,
pp. 167-175,
01/01/1994
Copyright © 1994 by The American Society of Hematology

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