title: The differential impact of natural killer (NK) cell education via KIR2DL3 and KIR3DL1 on CCL4 secretion in the context of in-vitro HIV infection.
abstract: Carriage of certain inhibitory natural killer (NK) cell receptor (iNKR)/HLA ligand pairs is associated with protection from infection and slow time to AIDS implicating NK cells in HIV control. NK cells acquire functional potential through education, which requires the engagement of iNKRs by their human leucocyte antigen (HLA) ligands. HIV infection down-regulates cell surface HLA-A/B, but not HLA-C/E. We investigated how NK cell populations expressing combinations of the iNKRs NKG2A, KIR2DL3 (2DL3) and KIR3DL1 (3DL1) responded to autologous HIV infected CD4 (iCD4) cells. Purified NK cells from HIV-uninfected individuals were stimulated with autologous HIV iCD4 or uninfected CD4 T cells. Using flow cytometry we gated on each of the 8 NKG2A+/-2DL3+/-3DL1+/-populations and analysed all possible combinations of interferon (IFN)-γ, CCL4 and CD107a functional subsets responding to iCD4 cells. Infected CD4 cells induced differential frequencies of NKG2A+/-2DL3+/-3DL1+/-populations with total IFN-γ+, CCL4+and CD107a+functional profiles. 2DL3+NKG2A+NK cells had a higher frequency of responses to iCD4 than other populations studied. A higher frequency of 2DL3+NK cells responded to iCD4 from individuals that were not HLA-C1 homozygotes. These results show that 2DL3+NK cells are mediators of HIV-specific responses. Furthermore, responses of NK cell populations to iCD4 are influenced not only by NK cell education through specific KIR/HLA pairs, but also by differential HIV-mediated changes in HLA expression.
authors: Research Institute of the McGill University Health Centre (MUHC), Montreal, Quebec, Canada.|Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
authors: I
authors: I
authors: Lisovsky
authors: Research Institute of the McGill University Health Centre (MUHC), Montreal, Quebec, Canada.|Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
authors: G
authors: G
authors: Isitman
authors: Research Institute of the McGill University Health Centre (MUHC), Montreal, Quebec, Canada.|Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
authors: A
authors: A
authors: Tremblay-McLean
authors: Research Institute of the McGill University Health Centre (MUHC), Montreal, Quebec, Canada.|Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
authors: R
authors: R
authors: Song
authors: Research Institute of the McGill University Health Centre (MUHC), Montreal, Quebec, Canada.
authors: S
authors: S
authors: DaFonseca
authors: Research Institute of the McGill University Health Centre (MUHC), Montreal, Quebec, Canada.|Chronic Viral Illness Service, MUHC, Glen Site, Montreal, Quebec, Canada.|Department of Family Medicine, McGill University, Montreal, Quebec, Canada.
authors: B
authors: B
authors: Lebouchẻ
authors: Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.|Chronic Viral Illness Service, MUHC, Glen Site, Montreal, Quebec, Canada.|Division of Hematology, MUHC, Glen Site, Montreal, Quebec, Canada.
authors: J-P
authors: JP
authors: Routy
authors: Department of Family Medicine, Université de Montréal, Montreal, Quebec, Canada.|Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors: J
authors: J
authors: Bruneau
authors: Research Institute of the McGill University Health Centre (MUHC), Montreal, Quebec, Canada.|Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.|Chronic Viral Illness Service, MUHC, Glen Site, Montreal, Quebec, Canada.|Division of Clinical Immunology, MUHC, Montreal, Quebec, Canada.
authors: N F
authors: NF
authors: Bernard
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D054407:Chemokine CCL4 / Q000378:metabolism*; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D054344:Receptors, KIR2DL3 / Q000235:genetics / Q000378:metabolism*; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D054407:Chemokine CCL4; D006680:HLA Antigens; D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; C515083:KIR3DL1 protein, human; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1
keywords: HIV; KIR-HLA; NK cell education; NK cells; innate-immune responses