HIV-1 Selection by Epidermal Dendritic Cells during Transmission across Human Skin

doi:10.1084/jem.187.10.1623

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J. Exp. Med., Volume 187, Number 10, May 18, 1998 1623-1631

HIV-1 Selection by Epidermal Dendritic Cells during Transmission across Human Skin

By Jeanette C. Reece,^* Amanda J. Handley,^* E. John Anstee, Wayne A. Morrison,^§ Suzanne M. Crowe, and Paul U. Cameron^*

From the ^* Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia 3052; the Alfred Hospital, Prahran, Victoria, Australia 3181; the ^§ Department of Plastic Surgery, St. Vincent's Hospital, Melbourne, Victoria, Australia 3065; and the AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia 3078

Macrophage tropic HIV-1 is predominant during the initial viremia after person to person transmission of HIV-1 (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 entryand carriage to the lymphoid tissue. Human skin explants wereused to model HIV-1 selection that may occur at the skin or mucosalsurface. Macrophage tropic, but not T cell line tropic strainsof HIV-1 applied to the abraded epidermis were recovered fromthe cells emigrating from the skin explants. Dermis and epidermiswere separated by dispase digestion after virus exposure to determinethe site of viral selection within the skin. Uptake and transmissionto T cells of all HIV-1 isolates was found with the dermal emigrantcells, but only macrophage tropic virus was transferred by emigrantsfrom the epidermis exposed to HIV-1, indicating selection onlywithin the epidermis. CD3⁺, CD4⁺ T cells were found in both the dermal and epidermal emigrantcells. After cell sorting to exclude contaminating T cells, macrophagetropic HIV-1 was found in both the dermal emigrant dendritic cellsand in dendritic cells sorted from the epidermal emigrants. Theseobservations suggest that selective infection of the immatureepidermal dendritic cells represents the cellular mechanism thatlimits the initial viremia to HIV-1 that can use the CCR5 coreceptor.

Key words: Langerhans cells; dendritic cells; skin; HIV; tropism

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