Effect of age and CMV on NK cell subpopulations

Campos, Carmen; Pera, Alejandra; Sánchez-Correa, Beatriz; Alonso, Corona; Lopez-Fernandez, Isabel; Morgado, Sara; Tarazona, Raquel; Solana, Rafael

doi:10.1016/j.exger.2014.01.008

Cited by 101 publications

(90 citation statements)

References 48 publications

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“…However, this feature is likely unrelated to the differences detected in NK-cell phenotype, since the NK-cell population in the elderly appears to be characterized by a reduction of CD56 BR NK-cells, of NKp30 and NKp46 expression 17 with unchanged expression of NKG2A and perforin compared to younger individuals. 18 From a functional standpoint, peripheral NK-cells from patients with HCC showed lower IFNg production, but similar TNF-a and CD107a expression levels compared to controls.…”

Section: Discussionmentioning

confidence: 95%

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

et al. 2016

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(controls) were phenotypically characterized. Unsupervised clustering based on the frequency of cells expressing different phenotypic NK-cell markers segregated HCC patients into different cohorts that were compared for outcome. NK-cell cytokine production and cytotoxicity were compared between cohorts with different overall survival (OS) and time to disease recurrence (TTR). By multivariate analysis, age, Child-Pugh class and NK-cell phenotypic clustering could independently identify patients with significantly different OS. NK-cells from patients with better outcome expressed higher levels of cytotoxic granules and CD3z and lower levels of natural cytotoxic receptors (NCRs) that were co-expressed with the inhibitory receptor NKG2A known to negatively regulate NCR function. Cytotoxic function and IFNg production were significantly lower in the cohort of patients with worse outcome compared to controls (p < 0.05). Our results show a role for NK-cells in the control of HCC progression and survival providing the basis for the development of immunotherapeutic strategies to potentiate NK-cell response.

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Section: Discussionmentioning

confidence: 95%

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

et al. 2016

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“…42 Although we could not compare our data with a fully age-matched, low-HCMV prevalence cohort, the frequency of CD57…”

Section: Hcmvmentioning

confidence: 90%

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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“…Since the majority of elderly individuals are CMV seropositive, changes produced by CMV on NK cells are difficult to differentiate from those attributed to ageing per se. In this regard, an increased expression of the activating receptor CD94/NKG2C (but no significant differences in the expression of its inhibitory counterpart CD94/NKG2A receptor) associated with CMV seropositivity has been described, not only in total NK cells [45,56] but also in the CD56 dim CD16 + and CD56 − CD16 + NK cell subpopulations [12]. An increased expression of CD57 in the CD56 dim NK cell subpopulation from elderly donors has also been reported [6].…”

Section: The Phenotype Of Nk Cells Changes With Ageingmentioning

confidence: 95%

“…CD56 bright NK cells have been recently considered as immature NK cells, precursors of CD56 dim NK cells [55]. A minor subset of dysfunctional NK cells characterized by the expression of CD16 and the absence of CD56 has been described to be increased in different clinical conditions such as HIV infection and in ageing [12,50,75,82].…”

Section: Natural Killer Cells: Subpopulations Receptors and Functionsmentioning

confidence: 99%

“…An increase in the percentage [6,12,22,46] and absolute number [6,18] of total NK cells has been described in healthy ageing, associated with a decrease in immature CD56 bright NK cells [6,13,22], both CD56 bright CD16 − and CD56 bright CD16 + NK cells [12], and a decline, maintenance or expansion of the more mature CD56 dim CD16 + NK cell subset [6,12,25,37,78]. Recently, it has also been reported an increase in the percentage of CD56 − CD16 + NK cells from healthy individuals with age [12]. The decrease in the CD56 bright NK cell subpopulation in the elderly supports that ageing is associated with a decrease in the output of immature CD56 bright cells from the bone marrow and an expansion of mature long-lived CD56 dim NK cells [75].…”

Section: Age-associated Changes In the Frequency Of Nk Cellsmentioning

confidence: 99%

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Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies?

Sánchez-Correa

Campos

Pera

et al. 2015

Cancer Immunol Immunother

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Several age-associated changes in natural killer (NK) cell phenotype have been reported that contribute to the defective NK cell response observed in elderly patients. A remodelling of the NK cell compartment occurs in the elderly with a reduction in the output of immature CD56(bright) cells and an accumulation of highly differentiated CD56(dim) NK cells. Acute myeloid leukaemia (AML) is generally a disease of older adults. NK cells in AML patients show diminished expression of several activating receptors that contribute to impaired NK cell function and, in consequence, to AML blast escape from NK cell immunosurveillance. In AML patients, phenotypic changes in NK cells have been correlated with disease progression and survival. NK cell-based immunotherapy has emerged as a possibility for the treatment of AML patients. The understanding of age-associated alterations in NK cells is therefore necessary to define adequate therapeutic strategies in older AML patients.

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Effect of age and CMV on NK cell subpopulations

Cited by 101 publications

References 48 publications

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

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

Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies?

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