Functional HIVCXCR4 coreceptor on human epithelial Langerhans cells and infection by HIV strain X4

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.