The Journal of Experimental Medicine
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Published online 20 November 2000.
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© The Rockefeller University Press, 0022-1007/2000/11/1491/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 10, November 20, 2000 1491-1500

Original Article

Candidate Microbicides Block HIV-1 Infection of Human Immature Langerhans Cells within Epithelial Tissue Explants

Tatsuyoshi Kawamuraa, Sandra S. Cohena, Debra L. Borrisa, Elisabeth A. Aquilinoa, Svetlana Glushakovab, Leonid B. Margolisb, Jan M. Orensteinc, Robin E. Offordd, A. Robert Neurathe, and Andrew Blauvelta
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

Correspondence to: Andrew Blauvelt, Bldg. 10, Rm. 12N238, 10 Center Dr., MSC 1908, Bethesda, MD 20892-1908. Tel:301-402-4167 Fax:301-402-1439

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-1Ba-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-1Ba-L (an R5 HIV-1 strain) more efficiently infected LC–T cell cocultures when compared with HIV-1IIIB (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


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