title: The CD85j+ NK cell subset potently controls HIV-1 replication in autologous dendritic cells.
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 CD85j(-) 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 was still strongly stained by a recombinant CD85j protein. These results suggest that CD85j(+) NK cell inhibition of HIV-1 replication in MDDC is mainly mediated by CD85j interaction with an unknown ligand (distinct from HLA class I molecules) preferentially expressed on HIV-1-infected MDDC.
authors.affiliation: Unité de Régulation des Infections Rétrovirales, Institut Pasteur Paris France. scott@pasteur.fr
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
authors.forename: Vincent
authors.initials: V
authors.lastname: Arnold
authors.forename: Céline
authors.initials: C
authors.lastname: Didier
authors.forename: Tarek
authors.initials: T
authors.lastname: Kattan
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pirozzi
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000821:virology; D015658:HIV Infections / Q000473:pathology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000821:virology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D008024:Ligands; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D010641:Phenotype; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000737:chemistry; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008024:Ligands; D011971:Receptors, Immunologic; D011994:Recombinant Proteins