Targeting Natural Killer Cells for Improved Immunity and Control of the Adaptive Immune Response

Natural cause of death ( NK ) cells are critical for targeting and killing tumor, virus-infected and stressed cells as a member of the natural immune system. recently, NK cells have besides emerged as key regulators of adaptive immunity and have become a big therapeutic target for cancer immunotherapy and infection control. NK cells display a divers align of phenotypes and routine. Determining how NK cells explicate and are regulated is critical for understanding their function in both unconditioned and adaptive unsusceptibility. In this follow-up we discuss current research approaches into NK cell adaptive exemption and how these cells are being harnessed for improving cancer and inoculation outcomes .

NK Cell Cells Are Innate Immune Killers

Natural Killer ( NK ) cells are cytotoxic chondritic lymphoid cells that develop from a common progenitor of B and T cells ( Kondo et al., 1997 ; Abel et al., 2018 ). NK cells have the congenital ability to recognize both virally infected and tumor cells, play a key function in tumor net ( Rosenau and Moon, 1961 ; Smith, 1966 ; Herberman et al., 1975 ; Kiessling et al., 1975 ; Yang et al., 2006 ), and the primary immunological answer to viral infection ( Biron et al., 1999 ; Vidal et al., 2011 ). When cytotoxic NK cells are activated, they release cytolytic granules and secrete incendiary cytokines and chemokines that activate and recruit components of both the natural and adaptive immune answer ( Iannello and Raulet, 2013 ) .
NK cell energizing is governed by the ligand-receptor interactions of the activate and inhibitory receptors expressed on the NK cell surface ( Tassi et al., 2006 ; Lanier, 2008 ; Bryceson et al., 2011 ). The poise of activating and inhibitory signals controls NK cell activation and officiate ( MacFarlane and Campbell, 2006 ). NK cell activating receptors have well documented interactions with both viral ( Alsheikhly et al., 1985 ; Mandelboim et al., 2001 ; Jarahian et al., 2009 ) and tumor derived ligands ( Sivori et al., 1997 ; Vitale et al., 1998 ; Pende et al., 1999 ). NK cells besides have killer cell immunoglobulin-like receptors ( KIRs ) that are vital to the normal affair of NK cells and are critical for the education of NK cells. It is through these receptors that NK cells teach tolerance of self through HLA-I molecules, which serve as ligands to inhibitory KIRs ( Ljunggren and Karre, 1990 ; Campbell and Purdy, 2011 ). diversity of KIR genotypes among individuals that contribute to KIR-HLA interactions have implications for NK cell function and response against tumors and viruses .

NK Cells With Adaptive Immune Cell Properties

classically, NK cells are regarded as members of the natural immune system, but recent studies have elucidated that NK cells can display both adaptive and memory-like phenotypes. Antigen-specific NK cell memory was first gear described in T and B cell insufficient shiner displaying hapten-specific contact hypersensitivity ( CHS ) in skin cells after adopted remove of NK cells from a previously sensitized donor ( O’Leary et al., 2006 ).

In addition to NK cell memory against haptens, it was discovered that murine NK cell receptor Ly49H showed specificity for MCMV-derived m157 expressed in mouse ( Daniels et al., 2001 ; Lee et al., 2001 ; Arase et al., 2002 ). This interaction between host Ly49H and virally-derived m157 elicits the clonal expansion of MCMV-activated NK cells, adenine well as the doggedness of memory NK cells that possess increased responsiveness to m157 ( Dokun et al., 2001 ; Bubic et al., 2004 ; Sun et al., 2009 ). This was an exercise of NK cell memory that was defined by specific NK cell sense organ recognition of viral antigens. Additional adoptive transfer studies in mice have revealed that liver-resident NK cells have responded to several other pathogens including HSV-2 ( Abdul-Careem et al., 2012 ), Vaccinia virus ( Gillard et al., 2011 ) and Influenza A ( IAV ) ( Li et al., 2017 ). Both the hapten and MCMV murine models demonstrated the specific recognition of foreign antigens by NK cells that contributed to a memory-like recall reception but did not demonstrate if this occurred in humans and the extent NK cell memory contributed to virus see .
NK cell adaptive reaction can besides be mounted by try signals expressed by infect host cells ( Figure 1A ). In humans, hantavirus-infected endothelial cells have been shown to upregulate HLA-E, a ligand for NK cell activating receptor NKG2C, subsequently resulting in the expansion of NKG2C+ NK cells, and the perseverance of this subset up to 2 months post infection ( Bjorkstrom et al., 2011 ). similarly, HCMV infection of peripheral rake cells and fibroblast cells elicits expansion of NKG2C+CD57+CD56dimCD16+ circulating NK cells in humans in acute infection models ( Beziat et al., 2013 ; Newhook et al., 2017 ) .

Figure 1. NK cells and adaptive exemption. (A) NK cells can develop memory-like attributes in answer to infection ( left ) or cytokine stimulation ( right ). (B) NK cells have been shown to regulate adaptive immunity by targeting dendritic cells ( left ) that can change the quality of the T cell response and T follicular assistant cells ( right ) that can regulate B cell festering ( bodily hypermutation ) and officiate. (C) remedy handling of NK cell serve using soluble NK cell receptors that target tumor or viral infect cells to improve NK cell targeting ( acme left ) or monoclonal antibody antibodies that block or stimulate NK cell receptors ( top right ) to modulate NK cell function are under stream development. vaccine components such as adjuvants ( bottom ) could besides be utilized to generate CIML NK cells in vivo with a vaccine .

Simian-immunodeficiency virus ( SIV ) inoculation and infection models in rhesus macaques have provided testify that hepatic and splenic NK cells had the capacity to specifically target and kill SIV Gag and Env-specific dendritic cells ( DC ), and that this toss off was NKG2C-dependent ( Reeves et al., 2015 ). recently published datum by Nikzad et aluminum. demonstrated that human liver-resident NK cells in humanize BLT mouse displayed antigen-specific killing in vitro against HIV Env-loaded DC ‘s 14 days post vaccination with recombinant HIV Env ( Nikzad et al., 2019 ). furthermore, they demonstrated that human NK cell memory is durable in humans. Individuals that had Varicella Zoster Virus ( VSV ) infection in their youth were injected with a VSV-STA vaccine and had a significantly higher percentage of degranulating NK cells localizing at the site of injection, compared to controls. Another study demonstrated NK cell memory in Hepatitis B virus contagion and vaccination ( Wijaya et al., 2020 ). These findings provide much-needed tell that antigen-dependent memory NK cells may be induced in humans, and that NK cell memory might have the electric potential to persist decades after initial sensitization .

Cytokine-Induced Memory-Like NK Cells

NK cells can undergo specialization into memory-like effectors once exposed to versatile cytokines such as IL-12, IL-15, and IL-18 ( Figure 1A ). These cytokine-induced memory-like ( CIML ) NK cells display higher IFN-γ secretion upon re-challenge compared to their naïve counterparts, and has been demonstrated in both mice and humans ( Cooper et al., 2009 ; Romee et al., 2012 ; Keppel et al., 2013 ; Berrien-Elliott et al., 2015 ). CIML NK cells may besides be defined by up-regulation of CD25 ( Leong et al., 2014 ), a well as complete demethylation of IFN-γ promoter regions and early epigenetic changes ( Lee et al., 2015 ; Wiencke et al., 2016 ). indeed, IFN-γ promoter region demethylation of NK cells is besides observed in the expanding NKG2C+ NK cells of HCMV-infected individuals, autonomous of the bearing cytokine treatment ( Luetke-Eversloh et al., 2014 ; Schlums et al., 2015 ). This similarity might imply that CIML expansion and continuity might depend on HCMV infection and/or NKG2C+ expansion, and that CIML phenotypes can be evoked independent of cytokine discussion ( Goodier et al., 2016 ). One key difference in HCMV-expanded NKG2C+ NK cells is that in vitro or vaccine-induced CIML NK cells have been associated with expansion of less distinguish NK cells. CIML NK cells have been a key player in holocene developments in cancer immunotherapy and have shown enhanced killing against a variety of cancer cellular telephone lines in vitro, including leukemia and ovarian cancer ( Romee et al., 2012, 2016 ; Uppendahl et al., 2019 ). More recently, Romee et aluminum. demonstrated enhance killing of leukemic targets after adopted CIML transmit into patients with acute accent myeloid leukemia ( AML ) and have conducted a clinical trial evaluating the safety of ALT-803—an IL-15 superintendent agonist complex that activates NK cell and CD8 T cell function—in patients with hematologic malignancies who had suffered a get worse post-Hematopoietic cellular telephone transplant ( HCT ) ( Romee et al., 2016, 2018 ). Another ongoing clinical trial aims at evaluating the efficacy of adoptively transferred CIML NK cells in get worse AML patients after HCT ( NCT03068819 ). future studies optimizing the ex-vivo coevals of CIML NK cells for immunotherapy of cancer vitamin a well as determining if CIML NK cells can be generated in vivo through a vaccine, accessory, or other cytokine-stimulating molecule will be necessary to farther improvement this area of research in the clinic .

NK Cells Influence Adaptive Immunity Through Regulation of T and B Cells

NK cells and B cells have long been known to associate, given that NK cells mediate antibody-dependent cellular cytotoxicity ( ADCC ) through the NK cell Fc receptor, CD16. late tell suggests that NK cells impact B cell affinity growth and immune function ( Figure 1B ). recent reports by Rydyznski et alabama. have elucidated that murine NK cells mar humoral immunity through the inhibition of CD4 T follicular assistant ( Tfh ) and germinal center ( GC ) B cell expansion and function ( Rydyznski and Waggoner, 2015 ; Rydyznski et al., 2015, 2018 ). Using an NP-KLH ( 4-hydroxy-3-nitrophenylacetyl ; keyhole limpet hemocyanin ) conjugate model for immunization in shiner, they demonstrated that NK cell-depleted mouse, compared to control mouse, had higher Tfh and GC B cell populations, greater expansion of splenic germinal centers, and an increase in the product of NP-specific antibodies that displayed higher affinities for NP following immunization. NK cell damage of B cell affinity festering in mouse was shown to occur in a perforin-dependent manner, as perforin-deficient mouse displayed a like degree of affinity maturation as NK cell depleted mouse did ( Rydyznski et al., 2018 ). other studies have shown that NK cells immediately activate B cellular telephone IgG and IgM production, a well as facilitate immunoglobulin class-switching and can control HIV-1 neutralizing antibody responses ( Snapper et al., 1994 ; Gao et al., 2008 ; Bradley et al., 2018 ). conversely, NK cells have besides been shown to have inhibitory roles in B cell function. Poly : IC injection in mouse inhibited IgM elementary reply, via NK cell activation ( Abruzzo and Rowley, 1983 ). T-cell dependent ( IL-2 ) NK cell energizing has besides been shown to have negative outcomes for antibody production after EBV and pokeweed mitogen stimulation ( Rydyznski and Waggoner, 2015 ). In homo NK cell-B cell co-culture experiments, NK cells have been shown to activate B cell antibody production via TNFα ( Becker et al., 1990 ) and CD40-CD40 ligand interactions ( Blanca et al., 2001 ) .
Studies in humans and mice have revealed that NK cells indirectly influence the T cell repertoire via direct interaction with antigen presenting cells, most notably immature Dendritic Cells ( iDC ) and mature Dendritic Cells ( mDC ; Figure 1B ). human DC-NK cellular telephone cross-talk and subsequent energizing of both cell types was beginning reported in vitro, where it was reported that DC-NK cell interaction enhances NK cell activation and DC festering, with the former expressing IFN-γ, stimulating the latter to mature, secrete IL-12, and amplify formulation of the co-stimulatory molecule CD86 ( Gerosa et al., 2002 ). In subsequent studies, mDC-derived IL-12 was shown to enhance CD8 T cell responsiveness and energizing ( Mocikat et al., 2003 ; Adams et al., 2005 ). The inclination for NK cells to kill iDCs while sparing mDCs, termed “ DC editing ” is another exercise of indirect changes to T cell immunity modulated by NK cells ( Morandi et al., 2012 ; Ferlazzo and Moretta, 2014 ). The elimination of iDCs is hypothesized to enhance T cell prime, by decreasing rival between iDCs and mDCs which have the costimulatory molecules needed for T cell activation. In humans, this process is thought to be governed by ligand-receptor interactions of NKp30 ligands expressed on iDCs, and inhibitory KIR ligands expressed on mDCs ( Ferlazzo et al., 2002 ) .
During infection, NK cells target and kill infected host cells, which release antigen available for DC consumption. This enhancement of DC cross-presentation efficaciously improves cytotoxic T cell mediated unsusceptibility. After transfer of allogeneic B cells in shiner, NK cell kill of the B cells resulted in apoptotic bodies taken up and presented by dendritic cells ( Iyoda et al., 2002 ). NK cellular telephone killing of Ova-expressing splenocytes besides resulted in exhaust of antigen, leading to the enhancement of CD8 and CD4 T cell prim ( Krebs et al., 2009 ). Activated murine NK cells are besides able of shaping T cell unsusceptibility directly. After activation, murine NK cells localize to the lymph nodes where they release IFN-γ, eliciting CD4+ T cell differentiation into the Th1 subtype ( Martin-Fontecha et al., 2004 ) .

NK Cell Regulation of T Cell Immunity During Viral Infection

LCMV and MCMV infection studies in mice have produced variable star results outlining the effect NK cells have on T cells during acute accent and chronic viral infection. Waggoner et aluminum. demonstrated that NK cells targeted and killed CD4 T cells during LCMV infection in mouse ( Waggoner et al., 2011 ). however, other studies of LCMV infection have suggested that NK cells directly eliminated CD8 cells either through an NKG2D-dependent manner or another undefined mechanism during LCMV infection ( Soderquest et al., 2011 ; Lang et al., 2012 ). recently published data suggests that NK cells directly kill CD8 T cells during LCMV infection in mouse, and that this kill is NCR-1 dependent ( Pallmer et al., 2019 ). The bearing of NK cells during LCMV infection in mouse was reported to elicit T-cell exhaustion, and subsequently reduce both CD4 and CD8 T cell reply to LCMV, and that NK cell depletion enhances T-cell mediated viral clearance ( Cook and Whitmire, 2013 ). In chronic models of MCMV infection, TRAIL+ NK cells have been reported to target CD4 T cells in the salivary gland, which the authors suggest is to limit autoimmunity during chronic infection ( Schuster et al., 2014 ). other experiments showed that IL-10 secretion by NK cells during MCMV infection inhibited CD8 T cell reception ( Lee et al., 2009 ) .

Vaccinating for Memory NK Cell Generation

Vaccines have historically relied on eliciting antigen-specific effecter and memory B and T cells to protect against subsequent contagion, but for challenging pathogens such as HIV-1 and TB, alternative strategies to boost unsusceptibility must be pursued .
CIML NK cell generalization during inoculation has a open advantage over antigen-specific NK cell memory, as it is not restricted to certain antigens. CIML NK cells have been proven to be elicited after immunization with several human vaccines, including TIV, YF-17D, and BCG ( Marquardt et al., 2015 ; Goodier et al., 2016 ; Suliman et al., 2016 ; Darboe et al., 2017 ). IL-15 has been demonstrated to prime TIV-vaccinated homo PBMC to produce congenital myeloid cytokines, angstrom well as generate CIML NK cells that have enhanced responsiveness to H3N2 influenza virus ( Wagstaffe et al., 2019b ). The perseverance and functional significance of vaccine induced CIML NK cells during inoculation requires farther investigation .
Although the recent findings of antigen-specific human NK cell memory are utilitarian, there is a dearth of literature outlining how human NK cells mediate antigen-specific toss off vitamin a well as how hanker human NK cell memory can persist in vivo. Findings on VZV-specific NK cell memory was limited by the fact that VZV-naïve individuals are rare, and thus were not available to be used as controls in the Nikzad et alabama. learn. The HCMV-induced differentiation of CD56dimNKG2C+ into adaptive like NK cells was shown to occur via an epigenetic mechanism, however, it is not clear if all disease models that display NKG2C+ NK cell expansion go through the same epigenetic changes that HCMV infection elicits .
It is hypothesized that some models of vaccine-dependent, antigen-specific memory NK cells occur through genomic rearrangement, rather than the epigenetic mechanisms displayed in HCMV infection/host stress signal models. respective studies have elucidated the correlation between antigen-specific CD4 T cell derived IL-2 and improved NK cell reaction in a number of different vaccination models ( Figure 1C ) ( Horowitz et al., 2012 ; Jost et al., 2014 ; Goodier et al., 2016 ). therefore, the mechanisms of adaptive NK cell memory coevals must be studied on a pathogen-dependent basis, if they are to be implicated in inoculation .

Enhancing Classical NK Cell Effector Functions for Better Vaccination Outcomes

A roadblock inhibiting vaccine-induced NK cellular telephone effecter routine is the restrict reason of how these processes occur in humans, and how these processes vary across different homo vaccine models. To date, a lot of the cultivate concerning NK cell effecter serve has centered around IAV and HIV models in mice and humans. Prophylactic and curative vaccine trials need to investigate key NK cell effector functions—namely PAMP and myeloid cytokine-induced NK cell activation, DC edit, and NK cell ADCC initiation .
Pathogen-associated molecular patterns ( PAMPs ) are frequently incorporated as adjuvants in vaccines ( Miyaji et al., 2011 ). PAMP-induced NK cell energizing has been correlated with overall vaccine immunogenicity ( Feng et al., 2013 ; Martins et al., 2014 ). A recent report suggested that the presence of IFN-g derived from PAMP-induced activated human NK cells amplifies the proinflammatory cytokine visibility of dendritic cells ( Oth et al., 2018 ). Although these findings need to be further investigated in specific infection and inoculation models, they suggest that the presence of PAMPs in conjunction with IL-2, enhance DC editing, and thus could be a lend divisor to the enhance immunogenicity of PAMP-containing vaccines. future efforts to determine which adjuvant or combinations of adjuvants that elicit superior NK cell function that results in better protective adaptive immune responses should be considered for all vaccines to increase vaccine efficacy and lastingness .
Myeloid cell-derived cytokines ( IL-12, IL-15, IL-18, IL-27 ) ampere well as T-cell derived IL-2 have all been documented to be involved with NK cell prim and activation. As described earlier, the IL-12, IL-15, IL-18 cytokine cocktail activated IFN-γ construction in NK cells during inoculation. A late composition has demonstrated that IL-27 promotes murine NK cell cytotoxicity and IFN-g production in an NKG2D-dependent manner during influenza infection ( Kumar et al., 2019 ). Nanogram concentrations of IL-15 have been demonstrated to boost IL-12 production and boost human NK cell function after exposure to H3N2 in vitro ( Wagstaffe et al., 2018 ). many of these cytokines have been explored in terms of immunotherapy but have not been examined a extensively as adjuvants for vaccines against infectious disease. Influenza models would provide a commodious avenue to investigate the role that IL-27 plays in human models of influenza vaccination .
Improving NK cell ADCC via vaccination is besides a key finish for Influenza, HIV-1, and early viruses ( Hashimoto et al., 1983 ; Mielke et al., 2019 ). recently, it was demonstrated that IL-15 is adequate to of improving ADCC-mediated killing against HIV-infected cells in seropositive donor plasma, and HVTN-100 vaccine trial ( Fisher et al., 2019 ). In influenza-infected adults, ADCC antibodies particular to highly conserve viral proteins nucleoprotein ( NP ) and matrix 1 ( M1 ) were found for both H1N1 and H5N2 strains of IAV ( Vanderven et al., 2017 ). ADCC antibodies for M2, another highly conserved IAV protein, has been shown to elicit ADCC in mouse, however homo trials have not so far been conducted. Ebola-specific ADCC antibodies have been confirmed in vitro in homo PBMCs and NK cell lines. recently, it was reported that Ebola-specific ADCC is activated after respective inoculation schedules of Adenovirus type 26.ZEBOV and modified vaccinia Ankara ( MVA ) –BN-Filo ( Wagstaffe et al., 2019a ) .
Influenza and HIV remain persistent pathogens creditworthy for the deaths of millions every class. NK cellular telephone effector functions have been implicated in both disease models and should continue to be investigated. NK cells display direct recognition of influenza infect cells via interaction of NKp46 and hemagglutinin ( HA ). In mouse, NK cells have been observed to localize to the lymph nodes during primary reaction to influenza inoculation and have ultimately been observed to regulate antibody production in an NK cellular telephone IFN-g and DC IL-6 dependent manner ( Garcia et al., 2012 ; Chatziandreou et al., 2017 ; Farsakoglu et al., 2019 ). The demand mechanism behind the infection-induced IL-6 reaction remains indecipherable and should be investigated further in mouse. The mechanism by which NK cells baffle humoral exemption during influenza vaccination should be examined in mouse and humans in order to investigate if an influenza vaccine with allow accessory combination can elicit a exchangeable immune response as seen in the murine infection model. The positive effect that murine NK cells display during acute viral infection is interest, given that chronic HIV infection models have suggested that functional NK cells play an inhibitory role in humoral unsusceptibility both in mouse and humans—namely through prohibition of B cell festering and decreased HIV-1 broadly neutralizing antibody output ( Rydyznski et al., 2015, 2018 ; Bradley et al., 2018 ). In summation to cytokines and adjuvants, the use of soluble NK cell receptors and antibodies targeting activating or inhibitory NK cellular telephone receptors could be utilized to modulate NK cell affair and determine the adaptive immune reply during infection, autoimmunity and cancer ( Figure 1C ). The function that NK cells play in humoral exemption are dependent on the nature of an contagion ( acute vs. chronic ) and the types of adaptive immune responses that are required to be protective .

Closing Remarks

here, we have summarized how NK cell phenotype and function can be manipulated to improve unsusceptibility to vaccines and cancer, and how NK cells can influence other arms of unconditioned and adaptive unsusceptibility. future efforts should attempt to elicit memory-like NK cell phenotypes, while enhancing natural NK cell effector functions. Limiting NK cell phenotypes that negatively impact the generation of protective immune responses must besides be pursued. It should besides be noted that future inoculation efforts should not seek to replace aspects of cell-mediated and humoral unsusceptibility with NK cell-mediated immunity but search to modulate NK cell function in tandem with adaptive immunity .

Author Contributions

SP, EG, and TB wrote and edited the manuscript .


This work was supported by the NIH National Institute of Allergy and Infectious diseases R01-AI147778 and generous digest from philanthropic contributions to Children ‘s Mercy Kansas City .

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or fiscal relationships that could be construed as a potential conflict of interest .


Becker, J. C., Kolanus, W., Lonnemann, C., and Schmidt, R. E. ( 1990 ). Human natural killer whale clones enhance in vitro antibody output by tumor necrosis factor alpha and da gamma interferon. Scand. J. Immunol. 32, 153–162. department of the interior : 10.1111/j.1365-3083.1990.tb02905.x
PubMed Abstract | CrossRef Full Text | Google Scholar
Bjorkstrom, N. K., Lindgren, T., Stoltz, M., Fauriat, C., Braun, M., Evander, M., et aluminum. ( 2011 ). rapid expansion and long-run doggedness of raised NK cell numbers in humans infected with hantavirus. J. Exp. Med. 208, 13–21. department of the interior : 10.1084/jem.20100762
PubMed Abstract | CrossRef Full Text | Google Scholar
Blanca, I. R., Bere, E. W., Young, H. A., and Ortaldo, J. R. ( 2001 ). Human B cell activation by autologous NK cells is regulated by CD40-CD40 ligand interaction : role of memory B cells and CD5+ B cells. J. Immunol. 167, 6132–6139. department of the interior : 10.4049/jimmunol.167.11.6132
PubMed Abstract | CrossRef Full Text | Google Scholar
Bradley, T., Peppa, D., Pedroza-Pacheco, I., Li, D., Cain, D. W., Henao, R., et alabama. ( 2018 ). RAB11FIP5 construction and altered natural killer cell serve are associated with induction of HIV broadly neutralizing antibody responses. Cell 175, 387–399. department of the interior : 10.1016/j.cell.2018.08.064
PubMed Abstract | CrossRef Full Text | Google Scholar
Chatziandreou, N., Farsakoglu, Y., Palomino-Segura, M., D’Antuono, R., Pizzagalli, D. U., Sallusto, F., et aluminum. ( 2017 ). Macrophage death following influenza vaccination initiates the incendiary reaction that promotes dendritic cell function in the draining lymph lymph node. Cell Rep. 18, 2427–2440. department of the interior : 10.1016/j.celrep.2017.02.026
PubMed Abstract | CrossRef Full Text | Google Scholar
Cook, K. D., and Whitmire, J. K. ( 2013 ). The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection. J. Immunol. 190, 641–649. department of the interior : 10.4049/jimmunol.1202448
PubMed Abstract | CrossRef Full Text | Google Scholar
Daniels, K. A., Devora, G., Lai, W. C., O’Donnell, C. L., Bennett, M., and Welsh, R. M. ( 2001 ). Murine cytomegalovirus is regulated by a discrete subset of lifelike cause of death cells reactive with monoclonal antibody to Ly49H. J. Exp. Med. 194, 29–44. department of the interior : 10.1084/jem.194.1.29
PubMed Abstract | CrossRef Full Text | Google Scholar
Feng, H., Du, X., Tang, J., Cao, X., Han, X., Chen, Z., et alabama. ( 2013 ). enhancement of the immune responses to foot-and-mouth disease vaccination in mouse by oral administration of a fresh polysaccharide from the roots of Radix Cyathulae officinalis Kuan ( RC ). Cell Immunol. 281, 111–121. department of the interior : 10.1016/j.cellimm.2013.02.004
PubMed Abstract | CrossRef Full Text | Google Scholar
Ferlazzo, G., Tsang, M. L., Moretta, L., Melioli, G., Steinman, R. M., and Munz, C. ( 2002 ). Human dendritic cells activate resting natural killer ( NK ) cells and are recognized via the NKp30 sense organ by activated NK cells. J. Exp. Med. 195, 343–351. department of the interior : 10.1084/jem.20011149
PubMed Abstract | CrossRef Full Text | Google Scholar
Gao, N., Jennings, P., and Yuan, D. ( 2008 ). Requirements for the natural cause of death cell-mediated trigger of IgG1 and IgG2a saying in B lymphocytes. Int. Immunol. 20, 645–657. department of the interior : 10.1093/intimm/dxn021
PubMed Abstract | CrossRef Full Text | Google Scholar
Garcia, Z., Lemaitre, F., avant-garde Rooijen, N., Albert, M. L., Levy, Y., Schwartz, O., et alabama. ( 2012 ). Subcapsular sinus macrophages promote NK cellular telephone collection and energizing in answer to lymph-borne viral particles. Blood. 120, 4744–4750. department of the interior : 10.1182/blood-2012-02-408179
PubMed Abstract | CrossRef Full Text | Google Scholar
Gillard, G. O., Bivas-Benita, M., Hovav, A. H., Grandpre, L. E., Panas, M. W., Seaman, M. S., et alabama. ( 2011 ). Thy1+ NK [ corrected ] cells from vaccinia virus-primed mouse confer protective covering against cowpox virus challenge in the absence of adaptive lymphocytes. PLoS Pathog. 7 : e1002141. department of the interior : 10.1371/journal.ppat.1002141
PubMed Abstract | CrossRef Full Text | Google Scholar
Herberman, R. B., Nunn, M. E., Holden, H. T., and Lavrin, D. H. ( 1975 ). Natural cytotoxic responsiveness of mouse lymphoid cells against syngeneic and allogeneic tumors. II. characterization of effector cells. Int. J. Cancer 16, 230–239. department of the interior : 10.1002/ijc.2910160205

PubMed Abstract | CrossRef Full Text | Google Scholar
Horowitz, A., Hafalla, J. C., King, E., Lusingu, J., Dekker, D., Leach, A., et alabama. ( 2012 ). Antigen-specific IL-2 secretion correlates with NK cell responses after immunization of tanzanian children with the RTS, S/AS01 malaria vaccine. J. Immunol. 188, 5054–5062. department of the interior : 10.4049/jimmunol.1102710
PubMed Abstract | CrossRef Full Text | Google Scholar
Iyoda, T., Shimoyama, S., Liu, K., Omatsu, Y., Akiyama, Y., Maeda, Y., et aluminum. ( 2002 ). The CD8+ dendritic cell subset selectively endocytoses dying cells in acculturation and in vivo. J. Exp. Med. 195, 1289–1302. department of the interior : 10.1084/jem.20020161
PubMed Abstract | CrossRef Full Text | Google Scholar
Kiessling, R., Klein, E., Pross, H., and Wigzell, H. ( 1975 ). “ Natural ” killer cells in the mouse. II. cytotoxic cells with specificity for mouse moloney leukemia cells. characteristics of the cause of death cell. Eur. J. Immunol. 5, 117–121. department of the interior : 10.1002/eji.1830050209
PubMed Abstract | CrossRef Full Text | Google Scholar
Lang, P. A., Lang, K. S., Xu, H. C., Grusdat, M., Parish, I. A., Recher, M., et aluminum. ( 2012 ). Natural killer cellular telephone energizing enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity. Proc. Natl. Acad. Sci. U.S.A. 109, 1210–1215. department of the interior : 10.1073/pnas.1118834109
PubMed Abstract | CrossRef Full Text | Google Scholar
Lee, S. H., Girard, S., Macina, D., Busa, M., Zafer, A., Belouchi, A., et alabama. ( 2001 ). susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily. Nat. Genet. 28, 42–45. department of the interior : 10.1038/ng0501-42
PubMed Abstract | CrossRef Full Text | Google Scholar
Lee, S. H., Kim, K. S., Fodil-Cornu, N., Vidal, S. M., and Biron, C. A. ( 2009 ). Activating receptors promote NK cell expansion for maintenance, IL-10 product, and CD8 T cell rule during viral infection. J. Exp. Med. 206, 2235–2251. department of the interior : 10.1084/jem.20082387
PubMed Abstract | CrossRef Full Text | Google Scholar
Leong, J. W., Chase, J. M., Romee, R., Schneider, S. E., Sullivan, R. P., Cooper, M. A., et alabama. ( 2014 ). Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional high-affinity IL-2 sense organ on human cytokine-induced memory-like natural killer cells. Biol. Blood Marrow Transplant. 20, 463–473. department of the interior : 10.1016/j.bbmt.2014.01.006
PubMed Abstract | CrossRef Full Text | Google Scholar
Luetke-Eversloh, M., Hammer, Q., Durek, P., Nordstrom, K., Gasparoni, G., Pink, M., et aluminum. ( 2014 ). Human cytomegalovirus drives epigenetic imprint of the IFNG locus in NKG2Chi natural cause of death cells. PLoS Pathog. 10 : e1004441. department of the interior : 10.1371/journal.ppat.1004441
PubMed Abstract | CrossRef Full Text | Google Scholar
Mandelboim, O., Lieberman, N., Lev, M., Paul, L., Arnon, T. I., Bushkin, Y., et aluminum. ( 2001 ). recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature 409, 1055–1060. department of the interior : 10.1038/35059110
PubMed Abstract | CrossRef Full Text | Google Scholar
Marquardt, N., Ivarsson, M. A., Blom, K., Gonzalez, V. D., Braun, M., Falconer, K., et aluminum. ( 2015 ). The human NK cellular telephone reception to yellow fever virus 17D is primarily governed by NK cell specialization independently of NK cellular telephone education. J. Immunol. 195, 3262–3272. department of the interior : 10.4049/jimmunol.1401811
PubMed Abstract | CrossRef Full Text | Google Scholar
Martins, K. A., Steffens, J. T., avant-garde Tongeren, S. A., Wells, J. B., Bergeron, A. A., Dickson, S. P., et alabama. ( 2014 ). Toll-like sense organ protagonist augments virus-like particle-mediated security from Ebola virus with transient immune activation. PLoS ONE 9 : e89735. department of the interior : 10.1371/journal.pone.0089735
PubMed Abstract | CrossRef Full Text | Google Scholar
Mocikat, R., Braumuller, H., Gumy, A., Egeter, O., Ziegler, H., Reusch, U., et alabama. ( 2003 ). Natural killer cells activated by MHC class I ( abject ) targets prime dendritic cells to induce protective CD8 T cell responses. Immunity 19, 561–569. department of the interior : 10.1016/s1074-7613 ( 03 ) 00264-4
PubMed Abstract | CrossRef Full Text | Google Scholar
Morandi, B., Mortara, L., Chiossone, L., Accolla, R. S., Mingari, M. C., Moretta, L., et alabama. ( 2012 ). Dendritic cell editing by activate natural cause of death cells results in a more protective cancer-specific immune response. PLoS ONE 7 : e39170. department of the interior : 10.1371/journal.pone.0039170
PubMed Abstract | CrossRef Full Text | Google Scholar
Oth, T., Habets, T., Germeraad, W. T. V., Zonneveld, M. I., Bos, G. M. J., and Vanderlocht, J. ( 2018 ). Pathogen realization by NK cells amplifies the proinflammatory cytokine production of monocyte-derived DC via IFN-gamma. BMC Immunol. 19:8. department of the interior : 10.1186/s12865-018-0247-y
PubMed Abstract | CrossRef Full Text | Google Scholar
Pallmer, K., Barnstorf, I., Baumann, N. S., Borsa, M., Jonjic, S., and Oxenius, A. ( 2019 ). NK cells negatively regulate CD8 T cells via lifelike cytotoxicity sense organ ( NCR ) 1 during LCMV infection. PLoS Pathog. 15 : e1007725. department of the interior : 10.1371/journal.ppat.1007725
PubMed Abstract | CrossRef Full Text | Google Scholar
Pende, D., Parolini, S., Pessino, A., Sivori, S., Augugliaro, R., Morelli, L., et alabama. ( 1999 ). designation and molecular word picture of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J. Exp. Med. 190, 1505–1516. department of the interior : 10.1084/jem.190.10.1505
PubMed Abstract | CrossRef Full Text | Google Scholar
Romee, R., Cooley, S., Berrien-Elliott, M. M., Westervelt, P., Verneris, M. R., Wagner, J. E., et aluminum. ( 2018 ). First-in-human phase 1 clinical cogitation of the IL-15 superagonist complex ALT-803 to treat get worse after transplant. Blood 131, 2515–2527. department of the interior : 10.1182/blood-2017-12-823757
PubMed Abstract | CrossRef Full Text | Google Scholar
Romee, R., Rosario, M., Berrien-Elliott, M. M., Wagner, J. A., Jewell, B. A., Schappe, T., et aluminum. ( 2016 ). Cytokine-induced memory-like natural killer cells parade enhance responses against myeloid leukemia. Sci. Transl. Med. 8:357ra123. department of the interior : 10.1126/scitranslmed.aaf2341
PubMed Abstract | CrossRef Full Text
Rosenau, W., and Moon, H. D. ( 1961 ). lysis of homologous cells by sensitize lymphocytes in weave culture. J. Natl. Cancer Inst. 27, 471–483 .
PubMed Abstract | Google Scholar
Schlums, H., Cichocki, F., Tesi, B., Theorell, J., Beziat, V., Holmes, T. D., et aluminum. ( 2015 ). Cytomegalovirus contagion drives adaptive epigenetic diversification of NK cells with altered signal and effecter function. Immunity 42, 443–456. department of the interior : 10.1016/j.immuni.2015.02.008
PubMed Abstract | CrossRef Full Text | Google Scholar
Schuster, I. S., Wikstrom, M. E., Brizard, G., Coudert, J. D., Estcourt, M. J., Manzur, M., et aluminum. ( 2014 ). TRAIL+ NK cells control CD4+ T cell responses during chronic viral infection to limit autoimmunity. Immunity 41, 646–656. department of the interior : 10.1016/j.immuni.2014.09.013
PubMed Abstract | CrossRef Full Text | Google Scholar
Snapper, C. M., Yamaguchi, H., Moorman, M. A., and Mond, J. J. ( 1994 ). An in vitro model for T cell-independent induction of humoral unsusceptibility. A necessity for NK cells. J. Immunol. 152, 4884–4892 .
PubMed Abstract | Google Scholar
Soderquest, K., Walzer, T., Zafirova, B., Klavinskis, L. S., Polic, B., Vivier, E., et alabama. ( 2011 ). Cutting edge : CD8+ T cell priming in the absence of NK cells leads to enhanced memory responses. J. Immunol. 186, 3304–3308. department of the interior : 10.4049/jimmunol.1004122
PubMed Abstract | CrossRef Full Text | Google Scholar
Tassi, I., Klesney-Tait, J., and Colonna, M. ( 2006 ). Dissecting natural killer whale cell energizing pathways through analysis of genic mutations in homo and sneak. Immunol. Rev. 214, 92–105. department of the interior : 10.1111/j.1600-065X.2006.00463.x
PubMed Abstract | CrossRef Full Text | Google Scholar
Vidal, S. M., Khakoo, S. I., and Biron, C. A. ( 2011 ). Natural killer whale cell responses during viral infections : flexibility and discipline of unconditioned immunity by know. Curr. Opin. Virol. 1, 497–512. department of the interior : 10.1016/j.coviro.2011.10.017

PubMed Abstract | CrossRef Full Text | Google Scholar
Vitale, M., Bottino, C., Sivori, S., Sanseverino, L., Castriconi, R., Marcenaro, E., et aluminum. ( 1998 ). NKp44, a novel triggering surface molecule specifically expressed by activated natural killer whale cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis. J. Exp. Med. 187, 2065–2072. department of the interior : 10.1084/jem.187.12.2065
PubMed Abstract | CrossRef Full Text | Google Scholar

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