Composition and dynamics of the uterine NK cell KIR repertoire in menstrual blood

Ivarsson, Martin A.; Stiglund, Natalie; Marquardt, Nicole; Westgren, Magnus; Gidlöf, Sebastian; Björkström, Niklas K.

doi:10.1038/mi.2016.50

Cited by 41 publications

(58 citation statements)

References 44 publications

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“…In fact, no statistically significant differences in CD57 (p=0.96) or NKG2A (p=0.75) expression were observed over time between placebo and vaccine groups. The temporally stable but heterogeneous expression of CD57 and NKG2A among individuals in the present study is consistent with prior observations (Ivarsson et al, 2017). As CMV infection is associated with increased expression of CD57 and down-regulation of NKG2A (Bjorkstrom et al, 2010), most notably among FcR neg (Zhang et al, 2013) and NKG2C high (Lopez-Verges et al, 2011) NK cells, the expression of these receptors was examined on the NK-cell subsets in vaccine trial participants (Figure 6B).…”

Section: Distinct Cd57 Expression On Fcr Neg Nk Cells In Absence Of CMVsupporting

confidence: 91%

Dynamic changes in natural killer cell subset frequencies in the absence of cytomegalovirus infection

Gyurova

Schlums

Sucharew

et al. 2019

Preprint

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Individuals lacking functional natural killer (NK) cells suffer severe, recurrent infections with cytomegalovirus (CMV), highlighting the critical role of NK cells in antiviral defense. Therefore, ongoing attempts to develop an efficacious vaccine to prevent CMV infection should potentially aim to elicit NK-cell antiviral responses as an accessory to conventional T-and B-cell based approaches. In this regard, CMV infection provokes marked phenotypic and functional differentiation of the NK-cell compartment, including development of adaptive NK cells that exhibit enhanced antiviral activity. We examined longitudinal blood samples collected from 40 CMV-seronegative adolescents to ascertain whether a CMV glycoprotein B (gB) vaccine in the absence of CMV infection can stimulate differentiation or expansion of CMV-associated subsets of NK cells. Study participants uniformly lacked the CMV-dependent NKG2C + subset of NK cells, suggesting that an adjuvanted CMV gB vaccine alone is an inadequate stimulus for sustained expansion of these cells. In contrast, we observed unexpected dynamic fluctuations in the frequency of NK cells lacking FcR, EAT-2, and SYK, which were independent of vaccination or CMV infection. Whereas FcR neg NK cells in CMV infection are reported to express increased levels of the maturation marker CD57, the FcR neg NK cells observed in our CMV-negative vaccine cohort express less CD57 than their FcR + counterparts. The FcR neg NK cells in CMV-negative individuals were also functionally distinct from this subset in CMV infection, exhibiting comparable IFN- production and degranulation as FcR + NK cells in response to cytokine or antibody-dependent stimuli. These results suggest that frequencies of some NK cell subsets may increase in response to unknown environmental or inflammatory cues distinct from that which occurs after CMV infection. Greater understanding of the nature of the signals driving CMVindependent accumulation of these subsets should permit development of mechanisms to facilitate vaccine-driven expansion of CMV-reactive NK cells.Vaccine | HCMV | Innate lymphoid cell | NK cell | Memory | CD56 | CD57 | FcR | SYK | NKG2C | EAT-2

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Section: Distinct Cd57 Expression On Fcr Neg Nk Cells In Absence Of CMVsupporting

confidence: 91%

Dynamic changes in natural killer cell subset frequencies in the absence of cytomegalovirus infection

Gyurova

Schlums

Sucharew

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Future studies will need to systematically analyse in-depth KIR repertoire of organ resident NK cells, which are known to display unique KIR repertoires, at least in the uterus and the liver. [184][185][186] When studying the KIR repertoire all the parameters that are known to influence KIR expression should be considered (Fig. 3), most of all KIR genotypes and cellular differentiation markers.…”

Section: Nk and T-cell Kir Repertoirementioning

confidence: 99%

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

et al. 2016

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SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

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“…However, whether hepatitis virus infection affects the prevalence of these expansions is unknown. Adaptive-like NK cell expansions have previously been identified based on deviations in KIR expression profiles, using statistical strategies such as the Chauvenet criterion (7, 18) and the Tukey’s range test (19), combined with cellular differentiation. As our analysis included patients with different hepatitis infections, likely affecting receptor expression to varying degrees, each group was analyzed separately.…”

Section: Resultsmentioning

confidence: 99%

“…Since expanded NK cell subsets have narrow KIR-repertoires often dominated by a single inhibitory receptor, different statistical strategies aimed at identifying outliers have previously been utilized to identify NK cell expansions (7, 18, 19). For cohorts significantly larger than ours, the Chauvenet criterion has been applied to select for NK cell expansions combined with cellular maturation (7, 18).…”

Section: Methodsmentioning

confidence: 99%

“…However, along with our smaller cohorts, the lower expression of some KIRs during hepatitis infections may affect selection. In line with how we previously identified NK cell expansions (19), a variation of the Tukey’s range test accounting for the cohort size was utilized to identify potential NK cell expansions. In more detail, CD56 dim NK cells were subdivided into subsets based upon their expression of NKG2A and NKG2C.…”

Section: Methodsmentioning

confidence: 99%

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Cytomegalovirus-Driven Adaptive-Like Natural Killer Cell Expansions Are Unaffected by Concurrent Chronic Hepatitis Virus Infections

et al. 2017

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Adaptive-like expansions of natural killer (NK) cell subsets are known to occur in response to human cytomegalovirus (CMV) infection. These expansions are typically made up of NKG2C+ NK cells with particular killer-cell immunoglobulin-like receptor (KIR) expression patterns. Such NK cell expansion patterns are also seen in patients with viral hepatitis infection. Yet, it is not known if the viral hepatitis infection promotes the appearance of such expansions or if effects are solely attributed to underlying CMV infection. In sizeable cohorts of CMV seropositive hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infected patients, we analyzed NK cells for expression of NKG2A, NKG2C, CD57, and inhibitory KIRs to assess the appearance of NK cell expansions characteristic of what has been seen in CMV seropositive healthy individuals. Adaptive-like NK cell expansions observed in viral hepatitis patients were strongly associated with CMV seropositivity. The number of subjects with these expansions did not differ between CMV seropositive viral hepatitis patients and corresponding healthy controls. Hence, we conclude that adaptive-like NK cell expansions observed in HBV, HCV, and/or HDV infected individuals are not caused by the chronic hepatitis infections per se, but rather are a consequence of underlying CMV infection.

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Composition and dynamics of the uterine NK cell KIR repertoire in menstrual blood

Cited by 41 publications

References 44 publications

Dynamic changes in natural killer cell subset frequencies in the absence of cytomegalovirus infection

Dynamic changes in natural killer cell subset frequencies in the absence of cytomegalovirus infection

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

Cytomegalovirus-Driven Adaptive-Like Natural Killer Cell Expansions Are Unaffected by Concurrent Chronic Hepatitis Virus Infections

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