Phenotypically and functionally distinct subsets contribute to the expansion of CD56−/CD16+ natural killer cells in HIV infection

Hong, Henoch S.; Eberhard, Johanna M.; Keudel, Phillip; Bollmann, Benjamin A.; Faried, Ahmad; Ballmaier, Matthias; Bhatnagar, Nupur; Zielinska‐Skowronek, Margot; Schmidt, Reinhold; Meyer-Olson, Dirk

doi:10.1097/qad.0b013e32833b556f

Cited by 42 publications

(56 citation statements)

References 33 publications

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“…Ϫ CD16 ϩ NK cells in chronic HIV-1 infection (17,19,20). These NK cell subset alterations were also evident in the distribution of NK cell subsets within CD8 ϩ CD3 Ϫ cells (Fig.…”

Section: Fig 1 High Absolute Number and High Frequencies Of Cd8mentioning

confidence: 79%

“…PBMCs were thawed and washed in PBS supplemented with FCS. Staining and flow cytometric analyses were performed as described before (19,25). Intracellular expression of perforin, granzyme B, and Ki-67 was analyzed ex vivo in unstimulated NK cells using a Fix and Perm kit (Life Technologies) following the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…Degranulation and intracellular cytokine staining assay. Functional NK cell assays were performed as described previously (19,26). Briefly, 10 5 sorted NK cells were stimulated with 100 ng/ml interleukin-12 (IL-12), 10 ng/ml IL-15, and/or K562 cells at an effector-to-target cell ratio of 2:1.…”

Section: Methodsmentioning

confidence: 99%

“…A number of reports have demonstrated phenotypic and functional changes in peripheral blood NK cells during HIV-1 infection in humans (16)(17)(18)(19)(20)(21). Progressive HIV-1 infection is associated with a decline in cytotoxic CD56 dim CD16 ϩ NK cells and an expansion of dysfunctional CD56 Ϫ CD16 ϩ NK cells (22,23).…”

Section: We Demonstrate That the Frequency Of Highly Functional Cd8 ؉mentioning

confidence: 99%

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High Frequencies of Polyfunctional CD8⁺NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

Faried

Hong

Jäckel

et al. 2014

J Virol

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؉ 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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“…Ϫ CD16 ϩ NK cells in chronic HIV-1 infection (17,19,20). These NK cell subset alterations were also evident in the distribution of NK cell subsets within CD8 ϩ CD3 Ϫ cells (Fig.…”

Section: Fig 1 High Absolute Number and High Frequencies Of Cd8mentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: We Demonstrate That the Frequency Of Highly Functional Cd8 ؉mentioning

confidence: 99%

See 2 more Smart Citations

High Frequencies of Polyfunctional CD8⁺NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

Faried

Hong

Jäckel

et al. 2014

J Virol

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“…Progressive HIV disease is associated clearly with increasingly impaired NK responses and the selective depletion of CD56 dim NK cells during chronic HIV-1 infection [112][113][114][115]. The loss of CD56 dim NK cells, the main circulating NK subset that mediates cytotoxicity, results in the enrichment of CD56 null NK cells with decreased function [113,[116][117][118]. HIV-1 replication also results in the altered expression of inhibitory and activating receptors on NK cells further impairing the lytic potential of the remaining NK pool [119][120][121].…”

Section: Nk Activity As a Correlate Of Resistance To Hiv-1 Infection mentioning

confidence: 99%

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

Tomescu

Abdulhaqq

Montaner

2011

Clinical and Experimental Immunology

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SummaryThe description of highly exposed individuals who remain seronegative (HESN) despite repeated exposure to human immunodeficiency virus (HIV)-1 has heightened interest in identifying potential mechanisms of HIV-1 resistance. HIV-specific humoral and T cell-mediated responses have been identified routinely in HESN subjects, although it remains unknown if these responses are a definitive cause of protection or merely a marker for exposure. Approximately half of HESN lack any detectible HIV-specific adaptive immune responses, suggesting that other mechanisms of protection from HIV-1 infection also probably exist. In support of the innate immune response as a mechanism of resistance, increased natural killer (NK) cell activity has been correlated with protection from infection in several highrisk cohorts of HESN subjects, including intravenous drug users, HIV-1 discordant couples and perinatally exposed infants. Inheritance of protective NK KIR3DL1 high and KIR3DS1 receptor alleles have also been observed to be over-represented in a high-risk cohort of HESN intravenous drug users and HESN partners of HIV-1-infected subjects. Other intrinsic mechanisms of innate immune protection correlated with resistance in HESN subjects include heightened dendritic cell responses and increased secretion of antiviral factors such as b-chemokines, small anti-viral factors and defensins. This review will highlight the most current evidence in HESN subjects supporting the role of epithelial microenvironment and the innate immune system in sustaining resistance against HIV-1 infection. We will argue that as a front-line defence the innate immune response determines the threshold of infectivity that HIV-1 must overcome to establish a productive infection.

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FcγRIII (CD16)‐mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32)

et al. 2014

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Monocytes are known to engage in reciprocal crosstalk with NK cells but their influence on NK-cell-associated antibody-dependent cellular cytotoxicity (ADCC) is not well understood. We demonstrate that in humans FcγRIII (CD16)-dependent ADCC by NK cells is considerably enhanced by monocytes, and that this effect is regulated by FcγRII (CD32) crosslinking in healthy individuals. It is known that during HIV-1 infection, NK cells are known to express low levels of CD16 and exhibit reduced ADCC.We show that immune regulation of CD16-mediated NK-cell cytotoxicity by monocytes through CD32 engagement is substantially disturbed in chronic progressive HIV-1 infection. Expression of activating isoform of CD32 represented a compensatory mechanism for reduced expression of CD16 on NK cells during HIV-1 infection. As a result, the regulation of NK-cell-associated ADCC by monocytes is skewed and eventually constitutes a novel factor that contributes to HIV-1-associated immune deficiency, dysregulation and pathogenesis. Our data therefore provide evidence, for the first time, that in humans monocytes act as a rheostat for FcγRIII-mediated NK-cell functions maintaining a well-balanced immune response. Keywords: ADCC r Fcγ receptors r Monocytes r NK cellsAdditional supporting information may be found in the online version of this article at the publisher's web-site Introduction NK cells are an important arm of innate immunity; they can kill tumor cells and virus-infected cells without prior sensitization, produce cytokines, and are involved in immune regulation. NK cells destroy their targets by natural cellular cytotoxicity (NCC)Correspondence: Dr. Dirk Meyer-Olson e-mail: dirk.meyer-olson@fachklinik-bad-pyrmont.de or antibody-dependent cellular cytotoxicity (ADCC) [1,2]. In antibody-mediated immune responses such as ADCC, Fc receptors bind to the Fc portion of antibody-coated target cells, which result in triggering of activating or inhibitory signaling pathways, thereby regulating the release of cytolytic granules and inflammatory mediators such as cytokines and chemokines [1,3]. Three different classes of Fcγ receptors have been described in humans, the high affinity FcγRI (CD64), and the medium-low affinity FcγRII (CD32), and FcγRIII (CD16) [4]. Various cell types such as NK cells, monocytes, neutrophils, and eosinophils are known C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 3368-3379 Innate immunity 3369 to perform ADCC. NK cells perform ADCC primarily via CD16, triggering target cell lysis and cytokine production [1,3]. Three different isoforms of CD32 are expressed on human cells: the activating receptors CD32A and CD32C, as well as the inhibitory receptor CD32B [3,5]. NK cells are thought to express mostly the activating isoform of the receptor, CD32C [6]. The role of Fc receptors in various diseases has been well documented: genetic polymorphisms in CD16 and CD32 have provided evidence for their implication in several infectious and autoimmune diseases highlighting...

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Phenotypically and functionally distinct subsets contribute to the expansion of CD56−/CD16+ natural killer cells in HIV infection

Abstract: These data indicate that expansion of CD56(-)/CD16(+) cells in HIV infection is driven by a distinct subset within this population with high expression of terminal differentiation marker with a phenotype resembling CD56(-)/CD16(+) NK cells.

Cited by 42 publications

References 33 publications

High Frequencies of Polyfunctional CD8⁺NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

High Frequencies of Polyfunctional CD8⁺NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

FcγRIII (CD16)‐mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32)

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Phenotypically and functionally distinct subsets contribute to the expansion of CD56−/CD16+ natural killer cells in HIV infection

Abstract: These data indicate that expansion of CD56(-)/CD16(+) cells in HIV infection is driven by a distinct subset within this population with high expression of terminal differentiation marker with a phenotype resembling CD56(-)/CD16(+) NK cells.

Cited by 42 publications

References 33 publications

High Frequencies of Polyfunctional CD8+NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

High Frequencies of Polyfunctional CD8+NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

FcγRIII (CD16)‐mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32)

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High Frequencies of Polyfunctional CD8⁺NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

High Frequencies of Polyfunctional CD8⁺NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression