the cd85j+ nk cell subset potently controls hiv-1 replication in autologous dendritic cellscd85j + nk细胞子集强有力地控制hiv - 1在自体树突细胞的复制.pdfVIP

The CD85j+ NK Cell Subset Potently Controls HIV-1 Replication in Autologous Dendritic Cells ´ ¤ ´ Daniel Scott-Algara*, Vincent Arnold, Celine Didier, Tarek Kattan, Gianluca Pirozzi , Franc¸oise Barre- Sinoussi, Gianfranco Pancino ´ ´ ´ Unite de Regulation des Infections Retrovirales, Institut Pasteur, Paris, France Abstract Natural killer (NK) cells and dendritic cells (DC) are thought to play critical roles in the first phases of HIV infection. In this study, we examined changes in the NK cell repertoire and functions occurring in response to early interaction with HIV- infected DC, using an autologous in vitro NK/DC coculture system. We show that NK cell interaction with HIV-1-infected autologous monocyte-derived DC (MDDC) modulates NK receptor expression. In particular, expression of the CD85j receptor on NK cells was strongly down-regulated upon coculture with HIV-1-infected MDDC. We demonstrate that CD85j+ NK cells exert potent control of HIV-1 replication in single-round and productively HIV-1-infected MDDC, whereas CD85j2 NK cells induce a modest and transient decrease of HIV-1 replication. HIV-1 suppression in MDCC by CD85j+ NK cells required cell-to-cell contact and did not appear mediated by cytotoxicity or by soluble factors. HIV-1 inhibition was abolished when NK-MDDC interaction through the CD85j receptor was blocked with a recombinant CD85j molecule, whereas inhibition was only slightly counteracted by blocking HLA class I molecules, which are known CD85j ligands. After masking HLA class I molecules with specific antibodies, a fraction of HIV-1 infected MDDC