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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3866-3875
The Susceptibility to X4 and R5 Human Immunodeficiency Virus-1
Strains of Dendritic Cells Derived In Vitro From
CD34+ Hematopoietic Progenitor Cells Is Primarily
Determined by Their Maturation Stage
Bruno Canque,
Youssef Bakri,
Sandrine Camus,
Micael Yagello,
Abdelaziz Benjouad, and
Jean Claude Gluckman
From ESA 7087 Université Paris 6-Centre Nationale de la
Recherche Scientifique, Laboratoire d'Immunologie Cellulaire de
l'Ecole Pratique des Hautes Etudes, hôpital
Pitié-Salpêtrière, Paris, France; and Laboratoire de
Biochimie, Faculté des Sciences, Rabat, Morocco.
Dendritic cells (DC) were sorted on day 8 from cultures of
CD34+ cells with stem cell factor/Flt-3 ligand/
granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor
necrosis factor- (TNF-)/interleukin-4 (IL-4). Exposing immature
CCR5+CXCR4lo/ DC to CCR5-dependent human
immunodeficiency virus (HIV)-1Ba-L led to productive and
cytopathic infection, whereas only low virus production occurred in
CXCR4-dependent HIV-1LAI-exposed DC. PCR analysis of the
DC 48 hours postinfection showed efficient entry of
HIV-1Ba-L but not of HIV-1LAI. CD40 ligand- or
monocyte-conditioned medium-induced maturation of
HIV-1Ba-L-infected DC reduced virus production by about 1 Log, while cells became CCR5. However,
HIV-1Ba-L-exposed mature DC harbored 15-fold more viral DNA than their immature counterparts, ruling out inhibition of virus
entry. Simultaneously, CXCR4 upregulation by mature DC coincided with
highly efficient entry of HIV-1LAI which, nonetheless,
replicated at the same low level in mature as in immature DC. In line
with these findings, coculture of HIV-1Ba-L-infected
immature DC with CD3 monoclonal antibody-activated autologous
CD4+ T lymphocytes in the presence of AZT decreased virus
production by the DC. Finally, whether they originated from
CD1a+CD14 or
CD1aCD14+ precursors, DC did not differ as
regards permissivity to HIV, although
CD1a+CD14 precursor-derived immature DC
could produce higher HIV-1Ba-L amounts than their
CD1aCD14+ counterparts. Thus, both DC
permissivity to, and capacity to support replication of, HIV is
primarily determined by their maturation stage.
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