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Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2001-12-0179.
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Blood, 1 September 2002, Vol. 100, No. 5, pp. 1780-1786
IMMUNOBIOLOGY
Subset of DC-SIGN+ dendritic cells in human blood
transmits HIV-1 to T lymphocytes
Anneke Engering,
Sandra J. van Vliet,
Teunis B. H. Geijtenbeek, and
Yvette van
Kooyk
From the Department of Molecular Cell Biology,
Vr e Universiteit Medical Center, Amsterdam, The
Netherlands.
The dendritic cell (DC)-specific molecule DC-SIGN is a receptor
for the HIV-1 envelope glycoprotein gp120 and is essential for the
dissemination of HIV-1. DC-SIGN is expressed by DCs, both monocyte-derived DCs and DCs in several tissues, including mucosa and
lymph nodes. To identify a DC-SIGN+ DC in blood that may be
involved in HIV-1 infection through blood, we have analyzed the
expression of DC-SIGN in human blood cells. Here we describe the
characterization of a subset of DCs in human blood, isolated from
T-/NK-/B-cell-depleted peripheral blood mononuclear cells (PBMCs) on
the basis of expression of DC-SIGN. This subset coexpresses
CD14, CD16, and CD33 and is thus of myeloid origin. In contrast
to CD14+ monocytes, DC-SIGN+ blood cells
display a DC-like morphology and express markers of antigen-presenting
cells, including CD1c, CD11b, CD11c, CD86, and high levels of major
histocompatibility complex (MHC) class I and II molecules.
This DC population differs from other described CD14
blood DC subsets. Functionally, DC-SIGN+ blood DCs are able
to stimulate proliferation of allogeneic T cells and can produce tumor
necrosis factor- (TNF-) and interleukin-6 (IL-6) upon activation
with lipopolysaccharide (LPS). When they encounter HIV-1, low
amounts of these blood DC-SIGN+ DCs enhance infection of T
lymphocytes in trans, whereas blood monocytes and CD14
blood DCs are not capable of transmitting HIV-1. Therefore
DC-SIGN+ blood DCs can be the first target for HIV-1 upon
transmission via blood; they can capture minute amounts of HIV-1
through DC-SIGN and transfer HIV-1 to infect target T cells in trans.
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