SIV REPLICATION AND THE DENDRITIC CELL

To evaluate the potential involvement of dendritic cells (DCs) in the mucosal transmission of HIV-1 we have used a model system of skin-deri ved DCs to study the cell-virus interactions in vitro. More recently w e have extended these studies to the macaque system to further investi gate DCs from a variety of more accessible tissues, particularly the m ucosae, The DCs isolated from macaque body surfaces exhibit an almost identical phenotype and morphology to mature human DCs, Both CD4(+) an d CD8(+) T cells are also present in the suspensions isolated from the se tissues, with some T cells being tightly bound to the DCs. As in th e human system, the skin-derived DCs support active replication of SIV in collaboration with syngeneic skin-derived T cells. Much of the vir us is produced by multinucleated syncytia, On separation of the cell s ubsets by cell sorting, it was revealed that most active viral replica tion occurs in the DC-T cell conjugate fraction. Virus growth is also detected within the DC-T cell mixtures isolated from the nasopharyngea l and vaginal mucosae, but not in those isolated from the cervical muc osa, This animal model is being used to further dissect the role of DC s in the transmission and pathogenesis of infection with immunodeficie ncy viruses.