Acquisition of Murine NK Cell Cytotoxicity Requires the Translation of a Pre-existing Pool of Granzyme B and Perforin mRNAs

Fehniger, Todd A.; Cai, Sheng F.; Cao, Xuefang; Bredemeyer, Andrew J.; Presti, Rachel; French, Anthony R.; Ley, Timothy J.

doi:10.1016/j.immuni.2007.04.010

Cited by 397 publications

(446 citation statements)

References 61 publications

Supporting

Mentioning

411

Contrasting

Order By: Relevance

“…To date, this heterogeneity has not been examined at the protein level for murine virus-specific CTL. Independent grz regulation is observed for resting murine NK cells that contain abundant grzA protein but little grzB [22]. Our analysis demonstrated that grzA was expressed only together with grzB in all of the virus-specific CTL populations examined.…”

Section: Discussionmentioning

confidence: 57%

“…1A). The CD8 À grzA 1 population is presumably NK cells [22]. Interestingly, CD8 1 grzA 1 CTL were always a subset of CD8 1 grzB 1 influenza A virus-specific CTL (Fig.…”

Section: Detection Of Grza Expression By Ctl Following Influenza a VImentioning

confidence: 86%

“…Therefore, it is currently unknown whether the transcriptional heterogeneity characteristic of virus-specific CTL is indeed reflected in distinct expression profiles for the corresponding cytolytic proteins. Using a recently described anti-murine grzA antibody [22], we examined grzA and grzB co-expression within murine influenza A virus-specific CTL. Interestingly, there is considerable heterogeneity that can be related to the various pMHCI complexes that drive influenza A virus CTL clonal expansion and determine response magnitude.…”

Section: Frontlinementioning

confidence: 99%

See 2 more Smart Citations

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection

et al. 2009

View full text Add to dashboard Cite

CTL mediate anti-viral immunity via targeted exocytosis of cytolytic granules containing perforin and members of the granzyme (grz) serine protease family. Here, we provide the first analysis of grzA protein expression by murine anti-viral CTL. During the progression of influenza A virus infection, CTL expressed two divergent cytolytic phenotypes: grzA À B 1 and grzA 1 B 1 . CTL lacked grzA expression during the initial rounds of antigen-driven division. High levels of grzA were expressed by influenza-specific CTL early post infection (day 6), particularly in tissues associated with the infected respiratory tract (bronchoalveolar lavage, lung). Following resolution of influenza infection, a small population of memory CTL expressed grzA. Interestingly, individual influenza A virus-derived epitopespecific CTL expressed different levels of grzA. The grzA expression hierarchy was determined to be K b PB1 703 5 D b F2 62 5 K b NS2 114 4D b NP 366 5 D b PA 224 and inversely correlated with CTL magnitude. Therefore following influenza infection, a CTL cytolytic hierarchy was established relating to the different profiles of antigen expression and relative immunodominance. Analysis of CTL grzA expression during influenza virus immunity has enabled a more detailed insight into the cytolytic mechanisms of virus elimination.

show abstract

Section: Discussionmentioning

confidence: 57%

“…1A). The CD8 À grzA 1 population is presumably NK cells [22]. Interestingly, CD8 1 grzA 1 CTL were always a subset of CD8 1 grzB 1 influenza A virus-specific CTL (Fig.…”

Section: Detection Of Grza Expression By Ctl Following Influenza a VImentioning

confidence: 86%

Section: Frontlinementioning

confidence: 99%

See 1 more Smart Citation

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Altogether, these results suggest the possibility that iNKT might regulate, at least to some extent, their cytokine secretion through such a translational mechanism. Whether it might apply to all cytokines/chemokines that are produced by iNKT cells and perhaps to their cytotoxic apparatus [36], remains to be determined.…”

Section: Cytokine and Chemokine Productionmentioning

confidence: 99%

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

359

399

View full text Add to dashboard Cite

SummaryNatural Killer T cells are a distinct lymphocyte lineage that regulates a broad range of immune responses. NKT cells recognize glycolipids presented by the non-classical MHC molecule CD1d. Structural insight into the TCR/glycolipid/CD1d tri-complex has revealed an unusual and unexpected mode of recognition. Recent studies have also identified some of the signaling events during NKT cell development that give NKT cells their innate phenotype. Pathogen-derived glycolipid antigens continue to be found, and new mechanisms of NKT cell activation have been described. Finally, NKT cells have been shown to be remarkably versatile in function during various immune responses. Whether these extensive functional capacities can be attributed to a single population sensitive to environmental cues or if functionally distinct NKT cell subpopulations exist remains unresolved.

show abstract

“…Type I interferons and cytokines that bind to the common γ-chain-containing receptors, such as IL-2 and IL-15, enhance NK cell responses. In mice, circulating NK cells do not express abundant perforin and granzyme B, until cytokine stimulation induces translation of pre-existing mRNA [80]. Recent experiments have suggested that such priming is delivered by contact with dendritic cells and trans-presentation of IL-15 [81*].…”

Section: Dynamic Tuning Of Nk Cell Effector Responsesmentioning

confidence: 99%

Line of attack: NK cell specificity and integration of signals

Bryceson

Long

2008

Current Opinion in Immunology

182

161

View full text Add to dashboard Cite

SummaryNatural killer (NK) cells possess potent cytolytic activity and secrete immune modulating cytokines. The large repertoire of NK cell receptors provides versatility for the identification of infected and transformed cells, and for their elimination by NK cells. NK cell responses also stimulate and regulate the adaptive arm of the immune system. We review current knowledge about the molecular specificity of NK cell receptors and about regulation of NK cell effector functions upon encounter with target cells. Mechanisms of recognition, interplay among receptors, signal integration, and dynamic finetuning of NK cell responses are discussed. New insights into molecular checkpoints for NK cell effector function are highlighted and underlying reasons for the complexity in NK cell recognition and signaling are proposed.

show abstract

Acquisition of Murine NK Cell Cytotoxicity Requires the Translation of a Pre-existing Pool of Granzyme B and Perforin mRNAs

Cited by 397 publications

References 61 publications

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Line of attack: NK cell specificity and integration of signals

Contact Info

Product

Resources

About