Phenotypic and Functional Characterization of Circulatory, Splenic, and Hepatic NK Cells in Simian Immunodeficiency Virus–Controlling Macaques

Vargas-Inchaustegui, Diego A.; Hait, Sabrina Helmold; Chung, Hye Kyung; Narola, Jigna; Hoang, Tanya; Robert-Guroff, Marjorie

doi:10.4049/jimmunol.1700586

Cited by 12 publications

(14 citation statements)

References 42 publications

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“…28,31 Nevertheless, close phenotypic analogies have been found between macaque and human NK cell subpopulations, and functional studies have revealed similar behavior in both species. [32][33][34][35] We previously uncovered the phenotypic complexity and diversity of innate myeloid cells in the blood and the impact of vaccinations on the dynamics of their subset composition by mass cytometry 27 in cynomolgus macaques immunized with a recombinant MVA HIV-B.…”

Section: Nk Cells Are Innate Lymphoid Cells That Can Constitutively Kmentioning

confidence: 99%

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NK cell immune responses differ after prime and boost vaccination

Palgen

Tchitchek

Huot

et al. 2019

Journal of Leukocyte Biology

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A better understanding of innate responses induced by vaccination is critical for designing optimal vaccines. Here, we studied the diversity and dynamics of the NK cell compartment after prime‐boost immunization with the modified vaccinia virus Ankara using cynomolgus macaques as a model. Mass cytometry was used to deeply characterize blood NK cells. The NK cell subphenotype composition was modified by the prime. Certain phenotypic changes induced by the prime were maintained over time and, as a result, the NK cell composition prior to boost differed from that before prime. The key phenotypic signature that distinguished NK cells responding to the boost from those responding to the prime included stronger expression of several cytotoxic, homing, and adhesion molecules, suggesting that NK cells at recall were functionally distinct. Our data reveal potential priming or imprinting of NK cells after the first vaccine injection. This study provides novel insights into prime‐boost vaccination protocols that could be used to optimize future vaccines.

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Section: Nk Cells Are Innate Lymphoid Cells That Can Constitutively Kmentioning

confidence: 99%

“…In addition, both human and macaque NK cells express NKp46, but in macaques, NKp46 may not be expressed by all NK cell subpopulations . Nevertheless, close phenotypic analogies have been found between macaque and human NK cell subpopulations, and functional studies have revealed similar behavior in both species …”

Section: Introductionmentioning

confidence: 99%

NK cell immune responses differ after prime and boost vaccination

Palgen

Tchitchek

Huot

et al. 2019

Journal of Leukocyte Biology

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“…Spleen and inguinal lymph node (LN) biopsies were dissected and passed through a 40 µm cell strainer after lysis of red blood cells (RBCs). The cells were washed and resuspended in R10 media (RPMI 1640 containing 10% FBS, 2 mM L-glutamine, 1% nonessential amino acids, 1% sodium pyruvate, and antibiotics) (30)(31)(32). Bone marrow cells were isolated by density gradient centrifugation on Ficoll.…”

Section: Sample Collection and Preparationmentioning

confidence: 99%

Overexpression of CD6 and PD-1 Identifies Dysfunctional CD8+ T-Cells During Chronic SIV Infection of Rhesus Macaques

et al. 2020

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Effective CD8 + T-cell responses play an important role in determining the course of SIV/HIV viral infection. Here we identified a unique population of dysfunctional CD8 + T-cells in lymphoid tissues and bronchoalveolar lavage (BAL) of rhesus macaques with chronic SIV infection characterized by co-expression of CD6 and PD-1. The frequency of CD6 and PD-1 co-expressing CD8 + T-cells was significantly increased in lymphoid tissues and BAL during chronic SIV infection compared to pre-infection levels. These CD6 + PD-1 + CD8 + T-cells displayed impaired proliferation, cytokine secretion and cytotoxicity compared to their CD6 − PD-1 + CD8 + T cell counterparts. The frequency of CD8 + PD-1 + and CD8 + CD6 − PD-1 + T-cells in the lymph node and bone marrow did not correlate with SIV viral load, whereas the frequency of CD8 + CD6 + PD-1 + T-cells positively correlated with SIV viral load in these tissues highlighting the contribution of CD6 to disease progression. CD6 + PD-1 + CD8 + T-cells expressed elevated levels of SHP2 phosphatase compared to CD6 − PD-1 + CD8 + T-cells providing a potential mechanism by which CD6 may induce T-cell dysfunction during chronic SIV infection. Combined targeting of CD6 and PD-1 effectively revived the CD8 + T-cell proliferative response in vitro suggesting a strategy for potential therapeutic benefit.

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“…The biopsy specimens were digested with collagenase (2 mg/ml; Sigma-Aldrich), and single cells were harvested as described (41). PBMCs were processed by density gradient centrifugation over Ficoll as described (27). PBMCs were frozen in FBS containing 10% DMSO and stored in liquid nitrogen until use.…”

Section: Sample Collectionmentioning

confidence: 99%

“…In the presence of HIV/SIV-specific Abs, NK cells exert potent antiviral responses to control infection (24)(25)(26). Similarly, in the SIV rhesus macaque model, NK cell-mediated ADCC activity was inversely correlated with viral loads (VLs) in chronically infected macaques (27). Polyfunctional humoral immune responses increase the antiviral capacity of innate immune cells, including NK cells of elite controllers (24).…”

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confidence: 99%

Differential Effect of Mucosal NKp44+ Innate Lymphoid Cells and Δγ Cells on Simian Immunodeficiency Virus Infection Outcome in Rhesus Macaques

Rahman

Enyindah-Asonye

et al. 2019

The Journal of Immunology

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NK cells are essential for controlling viral infections. We investigated NK cell and innate lymphoid cell (ILC) dynamics and function in rhesus macaque rectal tissue and blood following mucosal priming with replicating adenovirus (Ad)-SIV recombinants, systemic boosting with SIV envelope protein, and subsequent repeated low-dose intravaginal SIV exposures. Mucosal memory-like NK and ILC subsets in rectal and vaginal tissues of chronically infected macaques were also evaluated. No differences in NK cell or ILC frequencies or cytokine production were seen between vaccinated and Ad-empty/alum controls, suggesting responses were due to the Ad-vector and alum vaccine components. Mucosal NKp44 + ILCs increased postvaccination and returned to prelevels postinfection. The vaccine regimen induced mucosal SIV-specific Ab, which mediated Ab-dependent cellular cytotoxicity and was correlated with mucosal NKp44 + CD16 + ILCs. Postvaccination NKp44 + and NKp44 + IL-17 + ILC frequencies were associated with delayed SIV acquisition and decreased viremia. In chronically SIV-infected animals, NKp44 + ILCs negatively correlated with viral load, further suggesting a protective effect, whereas, NKG2A 2 NKp44 2 double-negative ILCs positively correlated with viral load, indicating a pathogenic role. No such associations of circulating NK cells were seen. Dg NK cells in mucosal tissues of chronically infected animals exhibited impaired cytokine production compared with non-Dg NK cells but responded to anti-gp120 Ab and Gag peptides, whereas non-Dg NK cells did not. Mucosal Dg NKp44 + and Dg DN cells were similarly associated with protection and disease progression, respectively. Thus, the data suggest NKp44 + ILCs and Dg cells contribute to SIV infection outcomes. Vaccines that promote mucosal NKp44 + and suppress double-negative ILCs are likely desirable.

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Phenotypic and Functional Characterization of Circulatory, Splenic, and Hepatic NK Cells in Simian Immunodeficiency Virus–Controlling Macaques

Cited by 12 publications

References 42 publications

NK cell immune responses differ after prime and boost vaccination

NK cell immune responses differ after prime and boost vaccination

Overexpression of CD6 and PD-1 Identifies Dysfunctional CD8+ T-Cells During Chronic SIV Infection of Rhesus Macaques

Differential Effect of Mucosal NKp44+ Innate Lymphoid Cells and Δγ Cells on Simian Immunodeficiency Virus Infection Outcome in Rhesus Macaques

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