Epstein-Barr Virus Coinfection in Children Boosts Cytomegalovirus-Induced Differentiation of Natural Killer Cells

Saghafian–Hedengren, Shanie; Sohlberg, Ebba; Theorell, Jakob; Carvalho-Queiroz, Claudia; Nagy, Noémi; Persson, Jan–Olov; Nilsson, Caroline; Bryceson, Yenan T.; Sverremark-Ekström, Eva

doi:10.1128/jvi.02382-13

Cited by 67 publications

(65 citation statements)

References 51 publications

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“…Moreover, anti-HCMV IgG titer was negatively correlated with the frequency of CD57 1 NK cells (supplemental Figure 4), suggesting that advanced NK cell differentiation may be associated with control of HCMV or vice versa. EBV serostatus, which has been associated with altered NK cell phenotype in HCMV-exposed Europeans, 7 had no significant effect on NK cell subset distribution, other than a minor increase in CD56 dim cell frequency (supplemental Figure 5A-G), supporting a recent paper suggesting that acute EBV coinfection has no major effect on NKG2C 1 CD57 1 NK cells. 30 …”

Section: Resultssupporting

confidence: 69%

“…Interestingly, HCMV and EBV coinfection did not affect NK cell phenotype or function. EBV coinfection has been associated with more extensive NK cell differentiation compared with HCMV alone in some European studies, 7 but not in a recent US study, 30 suggesting that perinatal HCMV infection alone is sufficient to drive NK cell differentiation or that infections other than EBV may also have an effect in this Gambian cohort. Of note, the biphasic kinetic of NK cell differentiation is not accompanied by a similar biphasic differentiation of T-cell populations, which is consistent with the suggestion that HCMV infection independently affects T-cell and NK cell populations.…”

mentioning

confidence: 99%

“…1 NK cells can be expanded by coculture with human cytomegalovirus (HCMV)-infected fibroblasts, 10 that HCMVseropositive individuals have increased frequencies of NKG2C 1 NK cells, [10][11][12][13] and that there is rapid expansion of CD57 1 NKG2C hi NK cells during acute HCMV infection 14 and in individuals infected with Epstein Barr virus (EBV), 7 hantavirus, 15 hepatitis viruses, 16 and chikungunya virus. 17 Among Caucasians, NK cell maturation is highly age-dependent.…”

Section: Introductionmentioning

confidence: 99%

“…2,5 Acquisition of CD57 is associated with onset of expression of NKG2C, although the codependence of these events and their implications for function are not understood. 7,8 Although the external drivers of NK cell differentiation are incompletely understood, inflammation, associated with infection or loss of immune homeostasis, plays a key role. 9 This view is supported by evidence that the late differentiation marker, CD57, can be induced on NK cells by high concentrations of IL-2, 5 that NKG2C…”

Section: Introductionmentioning

confidence: 99%

“…Although some of this is heterogeneity may be genetically determined and/or stochastic, 37 exposure to infections in addition to HCMV may also affect NK cell maturation. 7,15,17,56 Further studies are needed to determine whether this is simply a cytokine-driven expansion, and thus likely to occur in response to many acute inflammatory stimuli, or whether some pathogens express specific ligands for CD57…”

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confidence: 99%

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Rapid NK cell differentiation in a population with near-universal human cytomegalovirus infection is attenuated by NKG2C deletions

Goodier

White

Darboe

et al. 2014

Blood

103

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Key Points• HCMV infection in early life is associated with rapid phenotypic and functional differentiation of NK cells. • Emergence of CD571 NK cells is attenuated in children lacking NKG2C.Natural killer (NK) cells differentiate and mature during the human life course; human cytomegalovirus (HCMV) infection is a known driver of this process. We have explored human NK cell phenotypic and functional maturation in a rural African (Gambian) population with a high prevalence of HCMV. The effect of age on the frequency, absolute number, phenotype, and functional capacity of NK cells was monitored in 191 individuals aged from 1 to 49 years. Increasing frequencies of NK cells with age were associated with increased proportions of CD56 dim cells expressing the differentiation marker CD57and expansion of the NKG2C 1 subset. Frequencies of NK cells responding to exogenous cytokines declined with age in line with a decreased proportion of CD57 2 cells. These changes coincided with a highly significant drop in anti-HCMV IgG titers by the age of 10 years, suggesting that HCMV infection is brought under control as NK cells differentiate (or vice versa). Deletion at the NKG2C locus was associated with a gene dose-dependent reduction in proportions of CD94 1 and CD57 1 NK cells. Importantly, anti-HCMV IgG titers were significantly elevated in NKG2C 2/2 children, suggesting that lack of expression of NKG2C may be associated with altered control

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Section: Resultssupporting

confidence: 69%

mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Rapid NK cell differentiation in a population with near-universal human cytomegalovirus infection is attenuated by NKG2C deletions

Goodier

White

Darboe

et al. 2014

Blood

103

View full text Add to dashboard Cite

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OMIP‐098: A 26 parameter, 24 color flow cytometry panel for human memory NK cell phenotyping

Creegan,

Degler,

Paquin‐Proulx

et al. 2023

Cytometry Pt A

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Enhancement of cytokine‐driven NK cell IFN‐γ production after vaccination of HCMV infected Africans

et al. 2017

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Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine‐induced responses, we studied NK‐cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure. In contrast to populations with lower prevalence of HCMV infection, no significant enhancement of NK‐cell responses (IFN‐γ, CD107a, CD25) occurred after in vitro re‐stimulation of post‐vaccination NK cells with TIV or DTPiP antigens compared to pre‐vaccination baseline cells. However, both vaccinations resulted in higher frequencies of NK cells producing IFN‐γ in response to exogenous IL‐12 with IL‐18, which persisted for up to 6 months. Enhanced cytokine responsiveness was restricted to less differentiated NK cells, with increased frequencies of IFN‐γ+ cells observed within CD56brightCD57−, CD56dimCD57−NKG2C− and CD56dimCD57−NKG2C+ NK‐cell subsets. These data suggest a common mechanism whereby different vaccines enhance NK cell IFN‐γ function in HCMV infected donors and raise the potential for further exploitation of NK cell “pre‐activation” to improve vaccine effectiveness.

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Epstein-Barr Virus Coinfection in Children Boosts Cytomegalovirus-Induced Differentiation of Natural Killer Cells

Cited by 67 publications

References 51 publications

Rapid NK cell differentiation in a population with near-universal human cytomegalovirus infection is attenuated by NKG2C deletions

Rapid NK cell differentiation in a population with near-universal human cytomegalovirus infection is attenuated by NKG2C deletions

OMIP‐098: A 26 parameter, 24 color flow cytometry panel for human memory NK cell phenotyping

Enhancement of cytokine‐driven NK cell IFN‐γ production after vaccination of HCMV infected Africans

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