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Role of dendritic cells in HIV-1 replications.
Pope MJ; Frankel S; Wenig B; Hoffman L; Granelli-Piperno A; Steinman RM;
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:172. Unique

Dendritic cells are specialized antigen presenting cells that normally pick up antigens in nonlymphoid sites and traffic to the T cells of lymphoid organs to initiate cell-mediated immunity. Dendritic cells are located in and beneath the skin and the mucosal surfaces that are involved in the sexual and possibly perinatal transmission of HIV-1. We have analyzed the interaction of HIV-1 with skin-derived dendritic cells, as a more accessible model of the mucosal surfaces in the digestive and genital tracts. The cutaneous dendritic cells actively support a productive infection with HIV-1, but only in the presence of syngeneic cutaneous T cells. The dendritic cells fuse with CD4+ memory T cells to form syncytia. No antigens or mitogens are added to these cultures, and the cells are not in cycle, implying that dendritic cells can promote HIV-1 replication in the absence of formal antigen presentation and T cell activation. However, both of the major controls for the HIV-1 promoter are present within syncytia, since the dendritic cells contribute active NF-kB transcription factors while the T cells contribute active Sp1. A natural site in which dendritic cells and T cells normally are juxtaposed in vivo is the lymphoepithelium of the tonsil and adenoid. In a large series of cases, cells with intracelluar HIV gag [p24] protein were found within and beneath this mucosa, but not within the underlying lymphoid tissue. The infected cells included syncytia in all cases, and the syncytia expressed dendritic cell-restricted markers. Therefore dendritic cells promote the replication of HIV-1 within syncytia in tissue culture and in vivo. The most relevant pools of dendritic cells may be located at mucosal surfaces rather than the T cell areas of lymphoid organs.

Dendritic Cells/IMMUNOLOGY/*PHYSIOLOGY HIV Core Protein p24/BLOOD HIV-1/GENETICS/*PHYSIOLOGY Human Lymphocyte Transformation Promoter Regions (Genetics) Virus Replication/*PHYSIOLOGY ABSTRACT

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