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* Groupe Immunité des Muqueuses et Agents Pathogènes and
Centre de Cytométrie en Flux, University of Saint-Etienne; and
INSERM U346, Lyon, France
Correspondence: Prof. C. Genin, G.I.M.A.P., Faculté de Médecine, 15 rue Ambroise Paré, 42023 Saint-Etienne cédex 2, France. E-mail: geninc{at}univ-st-etienne.fr
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 expressed by fresh Langerhans cells isolated
and purified from epidermis. However, the percentage of Langerhans
cells expressing CXCR4 or CCR5 increased during maturation of the cells
in culture, especially in the presence of exogenous
granulocyte-macrophage colony-stimulating factor. To determine whether
CXCR4 was functional, freshly isolated Langerhans cells were infected
with HIV LAI, a T-cell-tropic strain, and p24 protein production was
measured in culture supernatants. p24 production was observed when
infected Langerhans cells were cocultured with SupT1 cells. However,
the presence of HIV provirus DNA was evidenced within the infected
Langerhans cells by nested PCR. Ultrastructural studies confirmed the
formation of syncytia when Langerhans cells were cocultured with SupT1
cells. Preincubation of Langerhans cells with azidothymidine or
SDF-1-
, a natural ligand for CXCR4, prevented infection. These data
demonstrated that CXCR4 is present on the surface of Langerhans cells
freshly isolated from human skin epidermis and that this expression is
functional.
Key Words: HIV • Langerhans cell • CXCR4 • CCR5 • CD4
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