HIV-1 SELECTION BY EPIDERMAL DENDRITIC CELLS DURING TRANSMISSION ACROSS HUMAN SKIN

Macrophage tropic HIV-1 is predominant during the initial viremia afte r person to person transmission of HIV-l (Zhu, T., H. Mo, N. Wang, D.S . Nam, Y. Cao, R.A. Koup, and D.D. Ho. 1993. Science. 261:1179-1181.), and this selection may occur during virus entry and carriage to the l ymphoid tissue. Human skin explants were used to model HIV-1 selection that may occur at the skin or mucosal surface. Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the abraded epider mis were recovered from the cells emigrating from the skin explants. D ermis and epidermis were separated by dispase digestion after virus ex posure to determine the site of viral selection within the skin. Uptak e and transmission to T cells of all HIV-1 isolates was found with the dermal emigrant cells, but only macrophage tropic virus was transferr ed by emigrants from the epidermis exposed to HIV-1, indicating select ion only within the epidermis. CD3(+), CD4(+) T cells were found in bo th the dermal and epidermal emigrant cells. After cell sorting to excl ude contaminating T cells, macrophage tropic HIV-1 was found in both t he dermal emigrant dendritic cells and in dendritic cells sorted from the epidermal emigrants. These observations suggest that selective inf ection of the immature epidermal dendritic cells represents the cellul ar mechanism that limits the initial viremia to HIV-1 that can use the CCR5 coreceptor.