title: High frequencies of polyfunctional CD8+ NK cells in chronic HIV-1 infection are associated with slower disease progression.
abstract: Natural killer (NK) cells are effector and regulatory innate immune cells and play a critical role in the first line of defense against various viral infections. Although previous reports have indicated the vital contributions of NK cells to HIV-1 immune control, nongenetic NK cell parameters directly associated with slower disease progression have not been defined yet. In a longitudinal, retrospective study of 117 untreated HIV-infected subjects, we show that higher frequencies as well as the absolute numbers of CD8(+) CD3(-) lymphocytes are linked to delayed HIV-1 disease progression. We show that the majority of these cells are well-described blood NK cells. In a subsequent cross-sectional study, we demonstrate a significant loss of CD8(+) NK cells in untreated HIV-infected individuals, which correlated with HIV loads and inversely correlated with CD4(+) T cell counts. CD8(+) NK cells had modestly higher frequencies of CD57-expressing cells than CD8(-) cells, but CD8(+) and CD8(-) NK cells showed no differences in the expression of a number of activating and inhibiting NK cell receptors. However, CD8(+) NK cells exhibited a more functional profile, as detected by cytokine production and degranulation.
  
  
  OBJECTIVE
  We demonstrate that the frequency of highly functional CD8(+) NK cells is inversely associated with HIV-related disease markers and linked with delayed disease progression. These results thus indicate that CD8(+) NK cells represent a novel NK cell-derived, innate immune correlate with an improved clinical outcome in HIV infection.
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany Hannover Biomedical Research School (HBRS), Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Fareed
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA.
authors.forename: Henoch S
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Jäckel
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Jablonka
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany Hannover Biomedical Research School (HBRS), Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: I-Na
authors.initials: IN
authors.lastname: Lu
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Nupur
authors.initials: N
authors.lastname: Bhatnagar
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Eberhard
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Bollmann
authors.affiliation: Pädiatrische Hämatologie und Onkologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ballmaier
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Margot
authors.initials: M
authors.lastname: Zielinska-Skowronek
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany Hannover Biomedical Research School (HBRS), Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany dirk.meyer-olson@fachklinik-bad-pyrmont.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer-Olson
mesh_terms: D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D008137:Longitudinal Studies; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D012189:Retrospective Studies
chemical_list: D017252:CD3 Complex; D016827:CD8 Antigens