Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Subset of DC-SIGN+ Dendritic Cells in Human Blood Transmits HIV-1 to T Lymphocytes

Abstract

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 DC, both monocyte-derived DC and DC 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 on human blood cells. Here, we describe the characterization of a subset of DC in human blood, isolated from T-/NK-/B-cell depleted PBMC based on the expression of DC-SIGN. This subset co-expresses CD14, CD16 and CD33 and are 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 MHC class I and II molecules. This DC population differs from other described CD14- blood DC subsets. Functionally, DC-SIGN+ blood DC are able to stimulate proliferation of allogeneic T cells and can produce TNF-[[aalpha]] and IL-6 upon activation with LPS. When encountering HIV-1 low amounts of these blood DC-SIGN+ DC enhance infection of T lymphocytes in trans, whereas blood monocytes and CD14- blood DC are not capable to transmit HIV-1. Therefore DC-SIGN+ blood DC can be the first target for HIV-1 upon transmission via blood that can capture minute amounts of HIV-1 through DC-SIGN and transfer HIV-1 to infect target T cells in trans.