Signatures of Human NK Cell Development and Terminal Differentiation

Luetke-Eversloh, Merlin V.; Killig, Monica; Romagnani, Chiara

doi:10.3389/fimmu.2013.00499

Cited by 121 publications

(110 citation statements)

References 61 publications

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“…That DCs and NK cells are not confined to the lungs in aSS patients suggests that NK cell-DC cross-talk could be at play in secondary lymphoid organs, rather than in target tissues. However, the significant phenotypic and functional changes of blood NK cells reported in the present study are consistent with the modulation of NK cell differentiation, previously described in humans (19,(30)(31)(32): NK cells from active aSS patients displayed a differentiated phenotype with low levels of NKp30, associated with high expressions of CD57 and ILT2. These results are further supported by the accuracy of the equation combining these three variables in predicting the activity of aSS.…”

Section: Discussionsupporting

confidence: 92%

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Hervier

Perez

Allenbach

et al. 2016

The Journal of Immunology

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Antisynthetase syndrome (aSS) is characterized by the association of interstitial lung disease and myositis with anti–tRNA synthetase autoantibodies. Immune mechanisms leading to aSS could be initiated in the lungs, but the role of NK cells has not yet been studied. Both extensive NK cell phenotype and functions were compared between 33 patients and 26 controls. Direct and redirected polyfunctionality assays (degranulation and intracellular production of TNF-α and IFN-γ) were performed spontaneously or after IL-12 plus IL-18 stimulation in the presence of K562 or P815 target cells, respectively. NK cells from inactive patients showed normal phenotype, whereas active aSS revealed a differentiated NK cell profile, as indicated by increased CD57 and Ig-like transcript 2 and an inability to produce IFN-γ (p = 0.002) compared with controls. Importantly, active aSS was more specifically associated with a significant NKp30 decrease (p = 0.009), although levels of mRNA and intracellular protein were similar in aSS and healthy controls. This NKp30 decrease was strongly correlated with reduced NK cell polyfunctionality in both direct and redirected killing assays with anti-NKp30 Abs (p = 0.009 and p = 0.03, respectively), confirming its important impact in aSS. Histological studies revealed massive infiltrations of NK cells inside the lungs of aSS patients (148 versus 11/mm2). Taken together, these data suggest that NK cells and NKp30 could play a role in aSS pathogenesis.

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Section: Discussionsupporting

confidence: 92%

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Hervier

Perez

Allenbach

et al. 2016

The Journal of Immunology

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“…37 Moreover, NK cells differentiate through the life course, reflecting the interplay of genes and environment. These adaptations substantially modify NK cell function 20,38,39 and are beginning to be associated with health outcomes. 9 Age is a major determinant of NK cell phenotype and function, 18-22 but it is not yet clear whether this is a result of primary, age-intrinsic processes or whether age is simply a marker for cumulative environmental exposures.…”

Section: Discussionmentioning

confidence: 99%

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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“…Although these cells are considered components of the innate immunity, some specific types of NK cells have been shown to proliferate in response to certain viral infections, including infection with HCMV. 9,10 Several markers that could be used to better characterize the different phases of NK cell maturation are being studied. Based on the expression of CD56, two subsets of these cells have been identified: CD56bright and CD56dim.…”

Section: 4mentioning

confidence: 99%

“…Within this context, some studies claim that CD57 -CD56bright NK cells are precursors of CD57 + CD56dim cells. 9,10 Thus, CD57 is a very useful marker of NK cell maturation and activation and has been used in experiments to consistently detect these cells.…”

Section: 4mentioning

confidence: 99%

Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts

et al. 2017

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The aim of this study was to compare the number of CD57 + natural killer (NK) cells and CD8 + T lymphocytes between periapical granulomas (PGs) and radicular cysts (RCs). Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification) and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8 + T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57 + NK cells and CD8 + T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively). Comparison of the number of CD57 + NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042). A larger number of CD57 + NK cells and CD8 + T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively). CD8 + T lymphocytes were more prevalent than CD57 + NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001). CD57+ NK cells and CD8 + T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8 + T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.

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Signatures of Human NK Cell Development and Terminal Differentiation

Cited by 121 publications

References 61 publications

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

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

Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts

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