title: Natural killer cell responses to dendritic cells infected by the ANRS HIV-1 vaccine candidate, MVAHIV.
abstract: Innate mechanisms are critical for the development of the host immune responses to antigen. Particularly, early interaction between natural killer (NK) cells and dendritic cells (DC) greatly impacts the establishment of both innate and adaptive immune responses. In this study, using an autologous in vitro co-culture system we analyzed the NK cell response against MVAHIV-infected DC as well as the subsequent ability of these MVAHIV-primed NK cells to control HIV-1 infection in autologous DC. We found that NK cells responded early to MVAHIV- or MVAWT-infected DC in terms of degranulation and cytokine production. After a 4-day priming of NK cells by MVAHIV- or MVAWT-infected DC we observed an enhanced proliferation and modulation in the NK cell receptor repertoire expression. Interestingly, we found that MVAHIV-primed NK cells had a significant higher ability to control HIV-1 infection in autologous DC compared to MVAWT-primed NK cells; and this enhanced anti-HIV-1 activity appeared to be HIV-specific as MVAHIV-primed NK cells did not have a better ability to control other viral infections or respond against tumoral cells. Furthermore, we observed that NK cell receptors NKG2D and NKp46 modulate the priming of NK cells. This data provides evidence that in vitro NK cells can be primed by viral vector-infected DC, in the context of a NK/DC culture, to specifically target viral infected cells.
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France. Electronic address: jean-saville.cummings@ndm.ox.ac.uk.
authors.forename: Jean-Saville
authors.initials: JS
authors.lastname: Cummings
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France.
authors.forename: Uriel Y
authors.initials: UY
authors.lastname: Moreno-Nieves
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France. Electronic address: vincent.Arnold@isped.u-bordeaux2.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Arnold
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Gilbert
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Yarbrough
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Didier
authors.affiliation: INSERM U955, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France. Electronic address: daniel.scott-algara@pasteur.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D015550:Cell Degranulation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000821:virology*; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015488:HIV Antigens; C527085:KLRK1 protein, human; C112260:NCR1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1
keywords: Dendritic cell; HIV-1; MVA–HIV; NK cell; NKp46