title: Elevated levels of invariant natural killer T-cell and natural killer cell activation correlate with disease progression in HIV-1 and HIV-2 infections.
abstract: In this study, we aimed to investigate the frequency and activation of invariant natural killer T (iNKT) cells and natural killer (NK) cells among HIV-1, HIV-2, or dually HIV-1/HIV-2 (HIV-D)-infected individuals, in relation to markers of disease progression.
  
  
  
  Whole blood samples were collected from treatment-naive HIV-1 (n = 23), HIV-2 (n = 34), and HIV-D (n = 11) infected individuals, as well as HIV-seronegative controls (n = 25), belonging to an occupational cohort in Guinea-Bissau.
  
  
  
  Frequencies and activation levels of iNKT and NK cell subsets were analysed using multicolour flow cytometry, and results were related to HIV-status, CD4 T-cell levels, viral load, and T-cell activation.
  
  
  
  HIV-1, HIV-D, and viremic HIV-2 individuals had lower numbers of CD4 iNKT cells in circulation compared with seronegative controls. Numbers of CD56 NK cells were also reduced in HIV-infected individuals as compared with control study participants. Notably, iNKT cell and NK cell activation levels, assessed by CD38 expression, were increased in HIV-1 and HIV-2 single, as well as dual, infections. HIV-2 viremia was associated with elevated activation levels in CD4 iNKT cells, CD56, and CD56 NK cells, as compared with aviremic HIV-2 infection. Additionally, disease markers such as CD4 T-cell percentages, viral load, and CD4 T-cell activation were associated with CD38 expression levels of both iNKT and NK cells, which activation levels also correlated with each other.
  
  
  
  Our data indicate that elevated levels of iNKT-cell and NK-cell activation are associated with viremia and disease progression markers in both HIV-1 and HIV-2 infections.
authors.affiliation: aDepartment of Medicine Huddinge, Center for Infectious Medicine bDepartment of Laboratory Medicine, Karolinska Institutet, Solna, Sweden cDepartment of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA dDepartment of Statistics, Lund University School of Economics and Management, Lund University, Lund, Sweden eNational Public Health Laboratory, Bissau, Guinea-Bissau fDepartment of Clinical Sciences Lund gDepartment of Translational Medicine hDepartment of Laboratory Medicine Lund, Lund University, Lund iDepartment of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Solna, Sweden. *Susanna M. Bächle and David F.G. Malone contributed equally to the writing of this article.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Bächle
authors.forename: David F G
authors.initials: DF
authors.lastname: Malone
authors.forename: Marcus
authors.initials: M
authors.lastname: Buggert
authors.forename: Annika C
authors.initials: AC
authors.lastname: Karlsson
authors.forename: Per-Erik
authors.initials: PE
authors.lastname: Isberg
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Biague
authors.forename: Hans
authors.initials: H
authors.lastname: Norrgren
authors.forename: Patrik
authors.initials: P
authors.lastname: Medstrand
authors.forename: Markus
authors.initials: M
authors.lastname: Moll
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.forename: Marianne
authors.initials: M
authors.lastname: Jansson
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006169:Guinea-Bissau; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*; D019562:Viral Load