SPLEEN AND BLOOD DENDRITIC CELLS IN HIV-1 INFECTION

Dendritic cells create optimal conditions for HIV replication by activ ating 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 f rom peripheral blood and spleen have similar characteristics in humans . Immature, round-shaped precursors, expressing CD4 and HLA-DR, but no t the costimulatory molecule CD80, are found predominantly. After cult ure, mature dendritic cells with a typical morphology, very efficient for stimulating a mixed lymphocyte reaction, can be isolated. These ce lls express CD80 and have a high HLA-DR expression, but they do not ex press CD4. Precursors and mature dendritic cells are negative for typi cal markers of the T, B and NK lineages and are negative for CD14, a m onocyte/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 prod uctive. This infection can contaminate cocultured CD4 T lymphocytes. E ven if cells from the dendritic lineage do not constitue a large quant itative reservoir of the virus, they may make a major contribution to CD4 T lymphocyte infection. At the onset of infection they may constit ue a port of entry with their CD4 receptor in the mucosa, then they ma y 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.