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The effect of in vitro human immunodeficiency virus infection on
dendritic-cell differentiation and function
B Canque, M Rosenzwajg, S Camus, M Yagello, ML Bonnet, M Guigon and JC Gluckman
Laboratoire de Biologie et Pathologie des Deficits Immunitaires, l'Ecole
Pratique des Hautes Etudes, Faculte de Medecine, Paris, France.
CD1a+ dendritic cells (DC) differentiate from a major population of
nonadherent CD13(hi)lin- cells that appear when human cord blood CD34+
hematopoietic progenitor cells are cultured with stem-cell factor,
granulocyte/macrophage (MA) colony-stimulating factor, and tumor necrosis
factor-alpha (TNF-alpha) for 5 days. CD13hilin- cells, which also comprise
MA and granulocyte precursors, are CD4+ and can thus be targets of human
immunodeficiency virus (HIV). Low replication was noted when these day 5
cells were infected with lymphotropic HIV-1LA1 (p24: < or = 4 ng/mL on
day 8 postinfection [PI]), while high virus production occurred with
MA-tropic HIV-1Ba-L, HIV-1Ada, or HIV-1-m-n. (p24: 50 to > or = 1,000
ng/mL). Strong cytopathicity (CPE) was then observed in nonadherent cells
as in adherent MA. However, FACS analysis on day 7 PI showed that HIV did
not affect differentiation of DC that survived CPE: apart from CD4
downmodulation related to HIV production, overall expression of CD40, CD80,
and CD86 costimulatory molecules, and of HLA-DR, was unchanged relative to
controls. At that time, the capacity of DC from HIV-infected cultures to
stimulate the mixed leukocyte reaction was only altered less than 10-fold.
Immunocytochemistry on day 7 PI showed that most HIV-infected cells were
included in syncytia that were stained by anti-CD1a, anti-S100, and
anti-CD14 antibodies, indicating that syncytia consisted of DC and cells of
the MA lineage. Polymerase chain reaction analysis of FACS- sorted CD1a+
cells confirmed that they harbored then HIV DNA. Viral DNA was also
detected in CD1a+ DC from noninfected cultures that had been exposed to HIV
only after sorting. Therefore, we examined whether in infected cultures DC
precursors were infected at the onset or if virus spread later from other
infected cells to differentiated DC. This was answered by showing that, 24
hours postexposure to HIV, viral DNA was preferentially detected in day 5
sorted CD13hilin- versus CD13hilin- cells, and that it was found in the
CD1a+ progeny of CD13(hi)lin- cells 48 hours later. In addition, HIV
replication did not affect myeloid clonogenic progenitors in day 0 to day 7
PI cultures, although viral DNA was detected in colony-forming
unit-granulocyte/macrophage (CFU- GM)/CFU-M colonies derived from day 3 and
7 PI cultures. Thus, precursors of DC and their progeny are susceptible to
HIV in vitro, but, apart from CPE, the effect of virus production on DC
differentiation or function is limited.
Volume 88,
Issue 11,
pp. 4215-4228,
12/01/1996
Copyright © 1996 by The American Society of Hematology
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