title: Switch from inhibitory to activating NKG2 receptor expression in HIV-1 infection: lack of reversion with highly active antiretroviral therapy.
abstract: BACKGROUND
  HIV-1 infection is characterized by increase in inhibitory receptors and loss of activating receptors on natural killer (NK) cells, resulting in loss of cell activity. Exceptionally, for an inhibitory receptor, the proportion of NK cells bearing CD94-NKG2A decreases during HIV-1 infection. It is not understood whether HIV-1 itself or other concomitant infections drive these changes.
  
  
  OBJECTIVE
  To investigate the relationship between HIV-1 viraemia and changes in C-type lectin-like receptor expression in NK cells and to investigate the effect of highly active antiretroviral therapy (HAART) on these changes.
  
  
  METHODS
  Three cohorts of patients were studied: (1) before, during and after treatment interruption in aviraemic and viraemic patients receiving HAART (n = 15); (2) HIV-1-positive treatment-naive individuals (n = 13); and (3) HIV-1-positive individuals receiving successful HAART for a minimum of 1 year without interruption (n = 11). Flow cytometry was used to study the expression of NKG2A before and after treatment interruption and to define expanded populations of NK cells in untreated and treated HIV-1-positive individuals. Assays were performed in vitro to assess the cytotoxicity of the expanded populations.
  
  
  RESULTS
  Increases in plasma HIV-1 RNA during treatment interruption in aviraemic HAART-treated individuals did not influence the proportion of NK cells carrying the complex CD94-NKG2A. Loss of NKG2A NK cells corresponded to the dramatic expansion of a distinct population of cells expressing a functional activating CD94-NKG2C receptor with skewed expression of killer cell immunoglobulin-like receptor family and natural cytotoxicity receptors.
  
  
  CONCLUSIONS
  Changes in the NK cell repertoire during HIV-1 infection were not a result of HIV-1 viraemia alone but resembled those associated with concomitant infections.
authors.affiliation: Department of Immunology, Imperial College, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Mela
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Burton
authors.forename: Nesrina
authors.initials: N
authors.lastname: Imami
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Alan
authors.initials: A
authors.lastname: Steel
authors.forename: Brian G
authors.initials: BG
authors.lastname: Gazzard
authors.forename: Frances M
authors.initials: FM
authors.lastname: Gotch
authors.forename: Martin R
authors.initials: MR
authors.lastname: Goodier
mesh_terms: D000914:Antibodies, Viral / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008875:Middle Aged; D014766:Viremia / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D037181:Lectins, C-Type