title: An NK Cell Population Lacking FcRγ Is Expanded in Chronically Infected HIV Patients.
abstract: We previously demonstrated that NK cells from HIV-infected individuals have elevated expression of activation markers, spontaneously degranulate ex vivo, and decrease expression of a signal-transducing protein for NK-activating receptors, FcRγ. Importantly, these changes were maintained in virologically suppressed (VS) individuals receiving combination antiretroviral therapy (cART). In this study, we show that loss of FcRγ is caused by the expansion of a novel subset of FcRγ(-)CD56(dim) NK cells with an altered activation receptor repertoire and biological properties. In a cross-sectional study, FcRγ(-) NK cells as a proportion of total CD56(dim) NK cells increased in cART-naive viremic HIV-infected individuals (median [interquartile range] = 25.9 [12.6-56.1] compared with 3.80 [1.15-11.5] for HIV(-) controls, p < 0.0001) and in VS HIV-infected individuals (22.7 [13.1-56.2] compared with 3.80 [1.15-11.5], p = 0.0004), with no difference between cART-naive and VS patients (p = 0.93). FcRγ(-) NK cells expressed no NKp30 or NKp46. They showed greater Ab-dependent cellular cytotoxicity activity against rituximab-opsonized Raji cells and in a whole-blood assay measuring NK responses to overlapping HIV peptides, despite having reduced CD16 expression compared with conventional NK cells. Their prevalence correlated with CMV Ab titers in HIV(-) subjects but not in HIV(+) individuals, and with the inflammatory marker CXCL10 in both groups. The expansion of a subset of NK cells that lacks NKp30 and NKp46 to ∼90% of CD56(dim) NK cells in some VS HIV(+) individuals may influence NK-mediated immunosurveillance in patients receiving cART.
authors: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia;
authors: Jingling
authors: J
authors: Zhou
authors: School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6009, Australia;
authors: Fathiah S
authors: FS
authors: Amran
authors: Department of Immunology and Microbiology, University of Melbourne, Melbourne, Victoria 3010, Australia;
authors: Marit
authors: M
authors: Kramski
authors: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia; School of Applied Sciences, Royal Melbourne Institute of Technology University, Melbourne, Victoria 3000, Australia;
authors: Tom A
authors: TA
authors: Angelovich
authors: Department of Infectious Diseases, Monash University, Melbourne, Victoria 3004, Australia; and.
authors: Julian
authors: J
authors: Elliott
authors: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia; Department of Infectious Diseases, Monash University, Melbourne, Victoria 3004, Australia; and.
authors: Anna C
authors: AC
authors: Hearps
authors: School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6009, Australia;
authors: Patricia
authors: P
authors: Price
authors: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia; Department of Infectious Diseases, Monash University, Melbourne, Victoria 3004, Australia; and Department of Immunology, Monash University, Melbourne, Victoria 3004, Australia anthonyj@burnet.edu.au.
authors: Anthony
authors: A
authors: Jaworowski
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D017452:Receptors, IgG