HIV-infected human Langerhans cells transmit infection to human lymphoid tissue ex vivo

Objectives: To create a novel ex vivo model for early biologic events invol ved in sexual transmission of HIV and to demonstrate that Langerhans cells (LC), the purported initial mucosal target cells for HIV, play a critical r ole in this process. Methods: Epidermal cells containing FC were isolated from normal-appearing skin of healthy volunteers and exposed to a panel of primary and laboratory -adapted R5- and X4-HIV isolates, washed and applied to the surfaces of all ogeneic tonsil tissue blocks. Viral replication was followed by measuring H IV p24 protein in culture supernatants by ELISA. Results: Both R5- and X4-HIV isolates could be transmitted by LC and establ ished high levels of infection in lymphoid tissue (p24 > 10 ng/ml). Depleti on of LC within epidermal cell suspensions abrogated the ability of HIV-exp osed suspensions to transmit virus to tonsil histocultures. Conclusions: Using a novel ex vivo model, human LC are shown for the first time to be the major epidermal cell type that is involved in transmission o f HIV infection to human lymphoid tissue. Importantly, this system could pr ove useful in further understanding LC trafficking and other early biologic al events involved in primary HIV Introduction infection. (C) 2000 Lippinco tt Williams & Wilkins.