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Original Article

^a Dermatology Branch, National Cancer Institute,
^b Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892
^c Department of Pathology, George Washington University, Washington, D.C. 20037
^d Departement de Biochime Medicale, Universite de Geneve, 1211 Geneva 4, Switzerland
^e The Lindsley F. Kimball Research Institute of The New York Blood Center, New York, New York 10021
Bldg. 10, Rm. 12N238, 10 Center Dr., MSC 1908, Bethesda, MD 20892-1908.301-402-1439301-402-4167

Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events, we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1_Ba-L infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.52%, range = 0.08–4.77%). HIV-1–infected LCs downregulated surface CD4 and CD83, whereas MHC class II, CD80, and CD86 were unchanged. For all HIV-1 strains tested, emigrated LCs were critical in establishing high levels of infection (0.1–1 µg HIV-1 p24 per milliliter) in cocultured autologous or allogeneic T cells. HIV-1_Ba-L (an R5 HIV-1 strain) more efficiently infected LC–T cell cocultures when compared with HIV-1_IIIB (an X4 HIV-1 strain). Interestingly, pretreatment of explants with either aminooxypentane-RANTES (regulated upon activation, normal T cell expressed and secreted) or cellulose acetate phthalate (potential microbicides) blocked HIV-1 infection of LCs and subsequent T cell infection in a dose-dependent manner. In summary, we document HIV-1 infection in single LCs after exposure to virus within epithelial tissue, demonstrate that relatively low numbers of these cells are capable of inducing high levels of infection in cocultured T cells, and provide a useful explant model for testing of agents designed to block sexual transmission of HIV-1.

Key Words: AIDS • dendritic cells • cellulose acetate phthalate • aminooxypentane-RANTES • transmission

T. Kawamura and S.S. Cohen contributed equally to this work.

© 2000 The Rockefeller University Press

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