Human CD34+ hematopoietic progenitor cells, stringently purified from the peripheral blood of 20 normal donors, showed an impaired survival and clonogenic capacity after exposure to either heat-inactivated human immunodeficiency virus (HIV) 1 (strain IIIB) or cross-linked envelope gp120. Cell cycle analysis, performed at different times in serum-free liquid culture, showed an accumulation in G0/G1 in HIV-1- or gp120-treated cells and a progressive increase of cells with subdiploid DNA content, characteristic of apoptosis. In blocking experiments with anti-transforming growth factor (TGF) beta 1 neutralizing serum or TGF-beta 1 oligonucleotides, we demonstrated that the HIV-1- or gp120-mediated suppression of CD34+ cell growth was almost entirely due to an upregulation of endogenous TGF-beta 1 produced by purified hematopoietic progenitors. Moreover, by using a sensitive assay on the CCL64 cell line, increased levels of bioactive TGF-beta 1 were recovered in the culture supernatant of HIV-1/gp120-treated CD34+ cells. Anti-TGF-beta 1 neutralizing serum or TGF-beta 1 oligonucleotides were also effective in inducing a significant increase of the plating efficiency of CD34+ cells, purified from the peripheral blood of three HIV-1-seropositive individuals, suggesting that a similar mechanism may be also operative in vivo. The relevance of these findings to a better understanding of the pathogenesis of HIV-1-related cytopenias is discussed.
Article|
January 01 1996
Inhibition of purified CD34+ hematopoietic progenitor cells by human immunodeficiency virus 1 or gp120 mediated by endogenous transforming growth factor beta 1.
G Zauli,
G Zauli
Institute of Human Anatomy, University of Ferrara, Italy.
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M Vitale,
M Vitale
Institute of Human Anatomy, University of Ferrara, Italy.
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D Gibellini,
D Gibellini
Institute of Human Anatomy, University of Ferrara, Italy.
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S Capitani
S Capitani
Institute of Human Anatomy, University of Ferrara, Italy.
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G Zauli
Institute of Human Anatomy, University of Ferrara, Italy.
M Vitale
Institute of Human Anatomy, University of Ferrara, Italy.
D Gibellini
Institute of Human Anatomy, University of Ferrara, Italy.
S Capitani
Institute of Human Anatomy, University of Ferrara, Italy.
Online Issn: 1540-9538
Print Issn: 0022-1007
J Exp Med (1996) 183 (1): 99–108.
Citation
G Zauli, M Vitale, D Gibellini, S Capitani; Inhibition of purified CD34+ hematopoietic progenitor cells by human immunodeficiency virus 1 or gp120 mediated by endogenous transforming growth factor beta 1.. J Exp Med 1 January 1996; 183 (1): 99–108. doi: https://doi.org/10.1084/jem.183.1.99
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