Efficient Virus Transmission from Dendritic Cells to CD4⁺T Cells in Response to Antigen Depends on Close Contact through Adhesion Molecules

Abstract

Monocyte-derived cultured dendritic cells (DCs) are potent antigen-presenting cells (APCs) and are susceptible to HIV-1_Laiinfection. Compared to the low level of virus production by HIV-1-infected DCs alone, a level of virus two to three orders of magnitude higher was produced by cocultivation of HIV-1-infected DCs with autologous resting CD4⁺T cells in the presence of a nominal antigen. In this coculture system, direct contact of HIV-1-infected DCs with T cells was crucial for efficient virus transmission and subsequent virus production. Blocking of the LFA-1/ICAM-1 or LFA-3/CD2 interaction between these cells substantially reduced virus production, without influence on IL-2 production by activated T cells. In contrast, cell–cell transmission of HIV between non-APCs and activated T cells was not blocked by an antibody against LFA-3. Since a low level of virus production by HIV-infected DCs was upregulated by cross-linking of CD40, it was suggested that not only focal adhesion, but also mutual activation of HIV-infected DCs and T cells through adhesion molecules, may potentiate virus transmission and production and that such activation signals to HIV may be distinct from signals responsible for IL-2 production in activated T cells.