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Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 62-73
Human CD34+ Cells Express CXCR4 and Its Ligand Stromal
Cell-Derived Factor-1. Implications for Infection by T-Cell Tropic
Human Immunodeficiency Virus
Alessandro Aiuti,
Lucia Turchetto,
Manuela Cota,
Arcadi Cipponi,
Andrea Brambilla,
Cinzia Arcelloni,
Rita Paroni,
Elisa Vicenzi,
Claudio Bordignon, and
Guido Poli
From Telethon Institute for Gene Therapy (TIGET); AIDS
Immunopathogenesis Unit, DIBIT; and Laboratory of Separative
Techniques, Scientific Institute H.S. Raffaele, Milan, Italy.
Human CD34+ hematopoietic progenitor cells obtained
from bone marrow (BM), umbilical cord blood (UCB), and mobilized
peripheral blood (MPB) were purified and investigated for the
expression of the chemokine receptor CXCR4 and its ligand, stromal
cell-derived factor-1 (SDF-1). CXCR4 was found present on the cell
surface of all CD34+ cells, although it was expressed at
lower density on MPB with respect to BM CD34+ cells.
Freshly isolated and in vitro-cultured CD34+ cells also
coexpressed SDF-1 mRNA, as determined by reverse
transcriptase-polymerase chain reaction (RT-PCR). Of interest,
CD34+/CD38+ committed progenitor cells,
unlike primitive CD34+/CD38 cells,
expressed SDF-1 mRNA. Supernatants from in vitro-cultured CD34+ cells contained substantial (3 to 8 ng/mL) amounts
of SDF-1 by enzyme-linked immunosorbent assay and induced migration of
CD34+ cells. Because CD34+ cells express
low levels of CD4, the primary receptor of the human immunodeficiency
virus (HIV), and CXCR4 is a coreceptor for T-cell tropic (X4) HIV
strains, we investigated the susceptibility of CD34+
cells to infection by this subset of viruses. Lack of productive infection was almost invariably observed as determined by a
conventional RT activity in culture supernatants and by real-time PCR
for HIV DNA in CD34+ cells exposed to both laboratory
adapted (LAI) and primary (BON) X4 T-cell tropic HIV-1 strain. Soluble
gp120 Env (sgp120) from X4 HIV-1 efficiently blocked binding of the
anti-CD4 Leu3a monoclonal antibody (MoAb) to either human
CD4+ T cells or CD34+ cells. In contrast,
sgp120 interfered with an anti-CXCR4 MoAb binding to human T
lymphocytes, but not to CD34+ cells. However, CXCR4 on
CD34+ cells was downregulated by SDF-1. These results
suggest that CXCR4 and its ligand SDF-1 expressed in
CD34+ progenitors may play an important role in
regulating the local and systemic trafficking of these cells. Moreover,
these findings suggest multiple and potentially synergistic mechanisms
at the basis of the resistance of CD34+ cells to X4 HIV
infection, including their ability to produce SDF-1, and the lack of
CXCR4 internalization following gp120 binding to CD4.

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