title: Candidate microbicides block HIV-1 infection of human immature Langerhans cells within epithelial tissue explants.
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.
authors.affiliation: Dermatology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kawamura
authors.forename: S S
authors.initials: SS
authors.lastname: Cohen
authors.forename: D L
authors.initials: DL
authors.lastname: Borris
authors.forename: E A
authors.initials: EA
authors.lastname: Aquilino
authors.forename: S
authors.initials: S
authors.lastname: Glushakova
authors.forename: L B
authors.initials: LB
authors.lastname: Margolis
authors.forename: J M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: R E
authors.initials: RE
authors.lastname: Offord
authors.forename: A R
authors.initials: AR
authors.lastname: Neurath
authors.forename: A
authors.initials: A
authors.lastname: Blauvelt
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002465:Cell Movement; D018946:Chemokine CCL5 / Q000031:analogs & derivatives* / Q000494:pharmacology; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000821:virology*; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D007801:Langerhans Cells / Q000821:virology*
chemical_list: D019380:Anti-HIV Agents; D018946:Chemokine CCL5; C111989:aminooxypentane-RANTES