I. Tchou et al., Functional HIVCXCR4 coreceptor on human epithelial Langerhans cells and infection by HIV strain X4, J LEUK BIOL, 70(2), 2001, pp. 313-321
HIV can cross the intact epithelium of genital mucosae via Langerhans cells
. Fresh Langerhans cells are known to express CD4 and CCR5. The presence of
CXCR4 on the surface of cultured but not freshly isolated Langerhans cells
has been described. In the present study, we demonstrate that CXCR4 was ex
pressed by fresh Langerhans cells isolated and purified from epidermis. How
ever, the percentage of Langerhans cells expressing CXCR4 or CCR5 increased
during maturation of the cells in culture, especially in the presence of e
xogenous granulocyte-macrophage colony-stimulating factor. To determine whe
ther CXCR4 was functional, freshly isolated Langerhans cells were infected
with HIV LAI, a T-cell-tropic strain, and p24 protein production was measur
ed in culture supernatants. p24 production was observed when infected Lange
rhans cells were cocultured with SupT1 cells. However, the presence of HIV
provirus DNA was evidenced within the infected Langerhans cells by nested P
CR. Ultrastructural studies confirmed the formation of syncytia when Langer
hans cells were cocultured with SupT1 cells. Preincubation of Langerhans ce
lls with azidothyinidine or SDF-1-alpha, a natural ligand for CXCR4, preven
ted infection. These data demonstrated that CXCR4 is present on the surface
of Langerhans cells freshly isolated from human skin epidermis and that th
is expression is functional.