Candidate microbicides block HIV-1 infection of human immature Langerhans cells within epithelial tissue explants

J Exp Med. 2000 Nov 20;192(10):1491-500. doi: 10.1084/jem.192.10.1491.

Abstract

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 microg 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.

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / virology
  • Cell Movement
  • Chemokine CCL5 / analogs & derivatives*
  • Chemokine CCL5 / pharmacology
  • Coculture Techniques
  • Epithelial Cells / virology*
  • HIV Infections / transmission*
  • HIV-1*
  • Humans
  • Langerhans Cells / virology*

Substances

  • Anti-HIV Agents
  • Chemokine CCL5
  • aminooxypentane-RANTES