Spleen and blood dendritic cells in HIV-1 infection.

Dendritic cells create optimal conditions for HIV replication by activating naive as well as memory T lymphocytes, and they express the CD4 receptor for the virus. The question of their role as a reservoir for the infection was crucial to understand the disease. Dendritic cells from peripheral blood and spleen have similar characteristics in humans. Immature, round-shaped precursors, expressing CD4 and HLA-DR, but not the costimulatory molecule CD80, are found predominantly. After culture, mature dendritic cells with a typical morphology, very efficient for stimulating a mixed lymphocyte reaction, can be isolated. These cells express CD80 and have a high HLA-DR expression, but they do not express CD4. Precursors and mature dendritic cells are negative for typical markers of the T, B and NK lineages and are negative for CD14, a monocyte/macrophage marker. In vivo infection of dendritic cells seems to be a rare event, (in the order of 1/1000 to 1/10000 infected cells) compared to that of CD4 T lymphocytes (1/10 to 1/1000), which are the major HIV-1 target. In vitro infection is possible, but not;very productive. This infection can contaminate cocultured CD4 T lymphocytes. Even if cells from the dendritic lineage do not constitue a large quantitative reservoir of the virus, they may make a major contribution to CD4 T lymphocyte infection. At the onset of infection they may constitue a port of entry with their CD4 receptor in the mucosa, then they may contaminate CD4 T lymphocytes by presenting this antigen back in the draining lymph nodes. Even when non-infected, they create foci where activated T lymphocytes can infect each other.