NK cells generate memory‐type responses to human cytomegalovirus‐infected fibroblasts

Newhook, Nicholas; Fudge, Neva J.; Grant, Michael D.

doi:10.1002/eji.201646819

Cited by 16 publications

(15 citation statements)

References 43 publications

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“…The relevance of HLA-E-NKG2C interactions for the expansion of adaptive NK cells has been demonstrated in vitro ( 2 , 74 , 75 , 76 ) and is supported by studies showing that NKG2C zygosity directly correlates with NKG2C surface levels and the size and distribution of NKG2C + NK cells in vivo ( 77 – 79 ).…”

Section: Hcmv-driven Priming and Expansion Of Adaptive Nk Cellsmentioning

confidence: 79%

HLA-E Peptide Repertoire and Dimorphism—Centerpieces in the Adaptive NK Cell Puzzle?

2018

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Adaptive Natural Killer (NK) cells, a heterogenous subpopulation of human NK cells with a unique phenotypic and functional signature, became arguably one of the central areas of interest in the field. While their existence seems closely associated with prior exposure to human cytomegalovirus (HCMV), many questions regarding their origin and regulation remain unanswered. However, a common denominator for the majority of adaptive NK cells is the expression of the activating heterodimeric receptor CD94/NKG2C that binds to HLA-E, a non-classical HLA molecule, that displays a comparably restricted expression pattern, very limited polymorphism and presents a distinct set of peptides. Recent studies suggest that—in analogy to T cell responses—peptides presented on HLA-E could play an unexpectedly decisive role for the biology of adaptive NK cells. Here, we discuss how this perspective on the CD94/NKG2C-HLA-E axis aligns with the existing literature and speculate about possible translational implication.

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Section: Hcmv-driven Priming and Expansion Of Adaptive Nk Cellsmentioning

confidence: 79%

HLA-E Peptide Repertoire and Dimorphism—Centerpieces in the Adaptive NK Cell Puzzle?

2018

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“…CD57 hi NKG2A − NKG2C − expanded populations have been observed in both NKG2C sufficient and deficient subjects; a recent study identified expansion of FcRγ – LIR‐1 + cells in both NKG2C + and NKG2C − NK cell populations among CMV + renal transplant patients, irrespective of their KLRC2 genotype, although the FcRγ – LIR‐1 + NKG2C − cells displayed greater ADCC against anti‐CMV antibody‐coated targets than did the FcRγ – LIR‐1 + NKG2C + population . A recent report analyzing expansion of NK cells against HCMV‐infected targets in vitro demonstrated expansion of NK cells independently of NKG2C expression . It is not yet clear what drives the expansion of these CD94/NKG2C‐ NK cells.…”

Section: Hcmv Infection Leads To Accumulation Of Terminally Differentmentioning

confidence: 99%

CMV and natural killer cells: shaping the response to vaccination

et al. 2017

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Cytomegaloviruses (CMVs) are highly prevalent, persistent human pathogens that not only evade but also shape our immune responses. Natural killer (NK) cells play an important role in the control of CMV and CMVs have in turn developed a plethora of immunoevasion mechanisms targeting NK cells. This complex interplay can leave a long-lasting imprint on the immune system in general and affect responses toward other pathogens and vaccines. This review aims to provide an overview of NK cell biology and development, the manipulation of NK cells by CMVs and the potential impact of these evasion strategies on responses to vaccination.Keywords: CMV r HCMV r Immune evasion r NK cells r Vaccination IntroductionCytomegaloviruses (CMVs) are beta-herpesviruses that establish life-long persistent infection of their hosts. After resolution of acute infection, the virus enters a state of latency during which very few genes are transcribed and no new viral progeny are being generated. Latency is interrupted by occasional reactivations of the virus and expression of genes associated with the lytic virus lifecycle [1]. The success of CMVs as pathogens is a consequence of multiple immunoevasion mechanisms such as downregulation of immunoreceptor ligands or expression of decoy molecules that they employ against every arm of the immune system, including NK cells, which play an important role in the early control of virally infected and malignant cells [2]. Individuals lacking NK cells may suffer from recurrent virus infections, most commonly caused by herpes viruses and papilloma viruses, as well as increased susceptibility to malignant tumors [3][4][5]. However, in other cases, there is no obvious clinical immunodeficiency associated with the Correspondence: Dr. Vanda Juranić Lisnić e-mail: vanda.juranic@medri.uniri.hr absence of NK cells, indicating redundancy with other immune compartments for distinct genetic deficiencies [6,7]. As NK cells also regulate other arms of the immune response, their modulation by CMV can have broader consequences for immunity [8]. For instance, the strength of the primary NK cell response against the virus can have a significant impact on the adaptive immune response, although the underlying mechanisms for this are not yet clear and vary according to host and virus genotypes [9,10]. CMV infection is associated with expansion of effector memory CD8 T cell clones that are sustained for the lifetime of the host and can comprise a significant percentage of the total CD8 T cell population in aging individuals [11]. Multiple lines of evidence in experimental animals and in humans which will be discussed in this review, now indicate that CMV infection leaves a similar long-lasting imprint on NK cell phenotype and function, affecting NK cell responses to other pathogens and to vaccination.Vaccines facilitate control and eradication of infectious diseases that have plagued humanity for centuries but new infections, * Current address: Eleanor M. Riley NK cell activity depends on a balance of signals from inhibit...

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“…Likewise, CMV infection drives the selective expansion of NKG2C + NK cells in rhesus macaques (Ram et al, 2018). Co-culture of human peripheral blood lymphocytes with HCMV-infected fibroblasts in vitro has been reported to drive the selective expansion of NKG2C + NK cells in some (Guma et al, 2006), although not all studies (Newhook et al, 2017).…”

Section: Cytomegalovirus (Cmv)mentioning

confidence: 99%

Memory and Memory-Like NK Cell Responses to Microbial Pathogens

Brillantes

Beaulieu

2020

Front. Cell. Infect. Microbiol.

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NK cells are cytotoxic lymphocytes that provide systemic defense against pathogens and malignancy. Although historically considered cells of the innate immune system, NK cells are now known to be capable of memory or memory-like immune responses in certain settings. Memory NK responses were initially reported over a decade ago in studies involving mouse models of cytomegalovirus infection and delayed-type hypersensitivity reactions to chemical haptens and viral antigens. Since then, a growing body of literature suggests that memory or memory-like NK cell responses may occur in a broader range of immunological settings, including in response to various viral and bacterial infections, and some immunization protocols. Memory-like NK cell responses have also now been reported in humans and non-human primates. Here, we summarize recent studies demonstrating memory or memory-like responses by NK cells in settings of infection and immunization against infectious agents.

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NK cells generate memory‐type responses to human cytomegalovirus‐infected fibroblasts

Cited by 16 publications

References 43 publications

HLA-E Peptide Repertoire and Dimorphism—Centerpieces in the Adaptive NK Cell Puzzle?

HLA-E Peptide Repertoire and Dimorphism—Centerpieces in the Adaptive NK Cell Puzzle?

CMV and natural killer cells: shaping the response to vaccination

Memory and Memory-Like NK Cell Responses to Microbial Pathogens

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