title: Phenotypical and functional profiles of natural killer cells exhibiting matrix metalloproteinase-mediated CD16 cleavage after anti-HIV antibody-dependent activation.
abstract: Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) has been linked to protection from HIV infection and slower progression towards AIDS. However, antibody-dependent activation of NK cells results in phenotypical alterations similar to those observed on NK cells from individuals with progressive HIV infection. Activation of NK cells induces matrix metalloproteinase (MMP)-mediated cleavage of cell surface CD16. In the present study we assessed the phenotype and functional profile of NK cells exhibiting post-activation MMP-mediated CD16 cleavage. We found that NK cells achieving the highest levels of activation during stimulation exhibit the most profound decreases in CD16 expression. Further, we observed that educated KIR3DL1(+) NK cells from human leucocyte antigen (HLA)-Bw4-carrying donors exhibit larger decreases in CD16 expression post-activation than the KIR3DL1(-) NK cell subset containing cells educated via other inhibitory receptor/ligand combinations and non-educated NK cells. Lastly, we assessed the ex-vivo expression of CD16 on educated KIR3DL1(+) NK cells and the KIR3DL1(-) NK cell subset from HLA-Bw4-carrying HIV-uninfected and HIV-infected donors. Suggestive of in-vivo activation of KIR3DL1(+) NK cells during HIV infection, CD16 expression was higher on KIR3DL1(+) than KIR3DL1(-) NK cells in uninfected donors but similar on both subsets in HIV-infected donors. These results are discussed in the context of how they may assist with understanding HIV disease progression and the design of immunotherapies that utilize antibody-dependent NK cell responses.
authors: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute, Melbourne, Victoria, Australia.
authors: C-C
authors: CC
authors: Tang
authors: Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
authors: G
authors: G
authors: Isitman
authors: Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Quebec, Canada.
authors: J
authors: J
authors: Bruneau
authors: Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Quebec, Canada.
authors: C
authors: C
authors: Tremblay
authors: Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
authors: N F
authors: NF
authors: Bernard
authors: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute, Melbourne, Victoria, Australia.|Melbourne Sexual Health Centre, Carlton, Victoria, Australia.
authors: S J
authors: SJ
authors: Kent
authors: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute, Melbourne, Victoria, Australia.
authors: M S
authors: MS
authors: Parsons
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity; D018450:Disease Progression; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D061251:Primary Cell Culture; D059748:Proteolysis; D012367:RNA, Viral / Q000097:blood*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D019562:Viral Load
chemical_list: D000906:Antibodies; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D012367:RNA, Viral; D017452:Receptors, IgG; D054341:Receptors, KIR3DL1; D020782:Matrix Metalloproteinases
keywords: AIDS; KIR3DL1; NK cell education
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