High frequencies of polyfunctional CD8+ NK cells in chronic HIV-1 infection are associated with slower disease progression
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High frequencies of polyfunctional CD8+ NK cells in chronic HIV-1 infection are associated with slower disease progression. / Ahmad, Fareed; Hong, Henoch S; Jäckel, Marc; Jablonka, Alexandra; Lu, I-Na; Bhatnagar, Nupur; Eberhard, Johanna M; Bollmann, Benjamin A; Ballmaier, Matthias; Zielinska-Skowronek, Margot; Schmidt, Reinhold E; Meyer-Olson, Dirk.
In: J VIROL, Vol. 88, No. 21, 11.2014, p. 12397-408.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - High frequencies of polyfunctional CD8+ NK cells in chronic HIV-1 infection are associated with slower disease progression
AU - Ahmad, Fareed
AU - Hong, Henoch S
AU - Jäckel, Marc
AU - Jablonka, Alexandra
AU - Lu, I-Na
AU - Bhatnagar, Nupur
AU - Eberhard, Johanna M
AU - Bollmann, Benjamin A
AU - Ballmaier, Matthias
AU - Zielinska-Skowronek, Margot
AU - Schmidt, Reinhold E
AU - Meyer-Olson, Dirk
N1 - Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PY - 2014/11
Y1 - 2014/11
N2 - UNLABELLED: 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.IMPORTANCE: 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.
AB - UNLABELLED: 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.IMPORTANCE: 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.
KW - CD3 Complex/analysis
KW - CD8 Antigens/analysis
KW - Cohort Studies
KW - Cross-Sectional Studies
KW - Disease Progression
KW - HIV Infections/immunology
KW - HIV-1/immunology
KW - Humans
KW - Killer Cells, Natural/chemistry
KW - Longitudinal Studies
KW - Lymphocyte Subsets/chemistry
KW - Retrospective Studies
U2 - 10.1128/JVI.01420-14
DO - 10.1128/JVI.01420-14
M3 - SCORING: Journal article
C2 - 25122796
VL - 88
SP - 12397
EP - 12408
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 21
ER -
