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Loss of primitive hematopoietic progenitors in patients with human
immunodeficiency virus infection
A Marandin, A Katz, E Oksenhendler, M Tulliez, F Picard, W Vainchenker and F Louache
INSERM U 362, Institut Gustave Roussy, Villejuif, France.
A number of hematologic abnormalities, including cytopenias, have been
observed in patients with human immunodeficiency virus (HIV) infection. To
elucidate their mechanisms, primitive cells from bone marrow aspirates of
21 patients with HIV-1 infection were quantitated by flow cytometry. The
mean percentage of CD34+ cells is not significantly altered in
HIV-1-infected patients in comparison with HIV-1- seronegative controls. In
contrast, two- and three-color immunofluorescence analysis showed that in
all HIV-1 samples, most CD34+ cells coexpressed the CD38 antigen. The
proportion of HIV-1- derived CD34+ cells that did not express the CD38
antigen was significantly lower (HIV-1+: mean, 1.73%; controls: mean, 14%;
P < .0005) than in controls. Moreover, of Thy-1+ cells, the proportion
of CD34+ cells was twofold lower in HIV-1-infected patients (HIV-1+: mean,
12%; controls, 25%, P < .0005), which suggests that phenotypically
primitive cells are depleted in HIV-1 infection. In vitro functional
analysis in long-term cultures of sorted CD34+ cells from seven HIV-1
patients showed that CD34+ cells from HIV-1 patients generated much fewer
colonies both in the nonadherent and adherent layers than CD34+ cells from
controls after 5 weeks of culture (10-fold and four-fold less,
respectively). Precise long-term culture initiating cell (LTC-IC) frequency
in the CD34+ cell population was determined in three patients by limiting
dilution and was markedly decreased in comparison to that of normal
controls (from twofold to > sevenfold decreased). To determine if
primitive cells were infected by HIV-1, both methylcellulose colonies
generated from long-term culture of CD34+ cells and various CD34+ cell
fractions purified by flow cytometry were evaluated for the presence of
HIV-1 by polymerase chain reaction (PCR). Progeny from long-term culture
was HIV-1-negative in three samples. In addition, using a sensitive PCR
technique, the HIV-1 genome could not be detected in CD34+, CD34+/CD38-,
and CD34+/CD4+ cells. These data show that hematologic disorders in HIV
disease may be the consequence of a deficit of primitive cells. However,
direct infection of these cells by HIV-1 does not seem to be responsible
for this defect.
Volume 88,
Issue 12,
pp. 4568-4578,
12/15/1996
Copyright © 1996 by The American Society of Hematology
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