Monocyte‐derived dendritic cells as a model for the study of HIV‐1 infection: Productive infection and phenotypic changes during culture in human serum

Dendritic cells (DC) have been implicated in the initial selection for macrophage‐tropic HIV‐1 during transmission and in the generation of high‐level virus replication during interactions with CD4 T cells. The role of DC as viral reservoirs and the extent of productive infection is unclear, but the ability to generate large numbers of DC from blood monocytes has produced a tractable model for study of DC–HIV‐1 interactions. When cultured in granulocyte–macrophage colony stimulating factor and IL‐4, sorted CD14+ monocytes rapidly lost phagocytic function for both 93 nm and 977 nm latex particles and developed the surface markers and function of DC. After 7 days, when returned to medium containing human serum without cytokines, some monocyte‐derived dendritic cells (MDDC) became adherent, but retained the costimulatory markers CD80 and CD86 and continued to express CD83 and CD40. The MDDC stimulated allogeneic CD4 T cells, did not express new macrophage markers and remained non‐phagocytic. With or without TNF‐α, MDDC generated in cytokines were infected by macrophage and T cell‐tropic virus and produced higher reverse transcriptase levels than did the autologous monocyte‐derived macrophages (MDM). When added to T cells, the infected MDDC were able to infect T cells with a wider range of viral isolates than were MDM.