title: Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals.
abstract: We have previously associated high natural killer (NK)-cell activity and protection against HIV-1 infection in Vietnamese exposed uninfected intravascular drug users (EUs). Considering that activating and inhibitory signals sensed by NK-cell receptors regulate NK-cell activation, we performed phenotypic and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) transcript analyses of the NK-cell receptor (NKR) repertoire in 25 EUs, 19 HIV(+) intravenous drug users, and 26 uninfected blood donors. Although NK-cell activation was not linked to a unique NKR repertoire in EUs, various patterns consistent with NK-cell activation were detected in EUs: high KIR3DS1/KIR3DL1 ratio associated with down-regulated KIR3DL1 transcript levels, KIR2DL3(+) low-affinity receptor expansion associated to group HLA-C1 ligand in 2DS2(-)/2DL2(-) EUs, enhanced NKG2C/NKG2A ratio, and increased CD69 expression. Remarkably, EUs exhibited high constitutive degranulation activity in the absence of exogenous stimulation, as shown by the CD107a assay. Furthermore, CD161 expression was increased within the CD107a(+) NK-cell compartment. Our results suggest that in response to viral exposition, particular genetic or regulated features of the NKR repertoire of EUs contribute to their high constitutive NK-cell potential. This might allow NK cells to generate a more rapid and effective immune response to HIV-1, thereby contributing to prevention toward infection.
authors.affiliation: Laboratoire Exploration NK, Laboratoire d'Hématologie, Centre Hospitalo-Universitaire Conception, Assistance Publique Hôpitaux de Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ravet
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
authors.forename: Elodie
authors.initials: E
authors.lastname: Bonnet
authors.forename: Hung Khiem
authors.initials: HK
authors.lastname: Tran
authors.forename: Ton
authors.initials: T
authors.lastname: Tran
authors.forename: Ngai
authors.initials: N
authors.lastname: Nguyen
authors.forename: Lien Xuan
authors.initials: LX
authors.lastname: Truong
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodorou
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
authors.forename: Pascale
authors.initials: P
authors.lastname: Paul
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D016022:Case-Control Studies; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011971:Receptors, Immunologic / Q000378:metabolism*; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1; D015819:Substance Abuse, Intravenous / Q000097:blood / Q000276:immunology
chemical_list: D000954:Antigens, Surface; C515078:KIR2DL3 protein, human; C515083:KIR3DL1 protein, human; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D052118:Lysosomal-Associated Membrane Protein 1; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1