期刊
JOURNAL OF VIROLOGY
卷 88, 期 21, 页码 12397-12408出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01420-14
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- Bundesministerium fur Bildung und Forschung, Stiftung Zukunfts- und Innovationsfonds Niedersachsen
- European AIDS Treatment Network
- Helmholtz-Zentrum fur Infektionsforschung [IG-SCID-TwinPro02]
- Hannover Biomedical Research School
- Deutsche Forschungsgemeinschaft [HO 4527/1-1]
- [DZIF TTU 04.804]
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.
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