Two alternate strategies for innate immunity to Epstein-Barr virus: One using NK cells and the other NK cells and γδ T cells

Djaoud, Zakia; Guethlein, Lisbeth A.; Horowitz, Amir; Azzi, Tarik; Nemat-Gorgani, Neda; Olive, Daniel; Nadal, David; Norman, Paul J.; Münz, Christian; Parham, Peter

doi:10.1084/jem.20161017

Cited by 61 publications

(96 citation statements)

References 51 publications

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“…It is conceivable, therefore, that the observed NKG2C + expansions are actually the result of a subclinical HCMV reactivation [142]. Primary EBV infection does not alter NKG2C expression in the NK cell repertoire, thus supporting the hypothesis that NKG2C expansions are an HCMV-specific phenomenon [82,83,143]. …”

Section: Mechanisms Of Nk Cell Diversification: Genetic and Environmementioning

confidence: 87%

“…During acute HCV infection, both NKp30 and NKp46 are upregulated exclusively on CD56 bright NK cells [149]. Additionally, NK cells stimulated with EBV-infected LCLs ex vivo have increased frequencies of NKp30 + cells [143,148]. NCR expression is also altered on CD56 neg NK cells in the setting of chronic infection.…”

Section: Mechanisms Of Nk Cell Diversification: Genetic and Environmementioning

confidence: 99%

“…TRAIL is required for IFN-γ-dependent suppression of tumor growth in vivo [175], and blockade of TRAIL activity in encephalomyocarditis virus (ECMV)-infected mice resulted in higher viral titers and earlier death [176]. TRAIL is upregulated by human NK cells during acute HCMV, EBV, and HCV infection, perhaps representing one mechanism by which NK cells provide early control of infection by these viruses [143,149,177]. …”

Section: Mechanisms Of Nk Cell Diversification: Genetic and Environmementioning

confidence: 99%

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Diversification of human NK cells: Lessons from deep profiling

Wilk

Blish

2018

Journal of Leukocyte Biology

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NK cells are innate lymphocytes with important roles in immunoregulation, immunosurveillance, and cytokine production. Originally defined on the functional basis of their "natural" ability to lyse tumor targets and thought to be a relatively homogeneous group of lymphocytes, NK cells possess a remarkable degree of phenotypic and functional diversity due to the combinatorial expression of an array of activating and inhibitory receptors. Diversification of NK cells is multifaceted: mechanisms of NK cell education that promote self-tolerance result in a heterogeneous repertoire that further diversifies upon encounters with viral pathogens. Here, we review the genetic, developmental, and environmental sources of NK cell diversity with a particular focus on deep profiling and single-cell technologies that will enable a more thorough and accurate dissection of this intricate and poorly understood lymphocyte lineage.

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Section: Mechanisms Of Nk Cell Diversification: Genetic and Environmementioning

confidence: 87%

Section: Mechanisms Of Nk Cell Diversification: Genetic and Environmementioning

confidence: 99%

Section: Mechanisms Of Nk Cell Diversification: Genetic and Environmementioning

confidence: 99%

See 1 more Smart Citation

Diversification of human NK cells: Lessons from deep profiling

Wilk

Blish

2018

Journal of Leukocyte Biology

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“…This finding suggests that the recommended influenza vaccination for allo-HCT recipients[102] might result in adaptive innate responses that are potentially cross-reactive towards other infections or malignant cells. Additionally, within EBV infected individuals, NK and γδT cell repertoires show differential, both redundant and non-redundant, activation patterns [103], which might also apply to CMV infection. Therefore, a next - generation vaccine is required to fulfill the needs synergistic activation of both subsets.…”

Section: 3 Potential Strategies To Simultaneously Enhance Nk and γδmentioning

confidence: 99%

“…NK and γδT cells share many innate features, yet they also have been shown to be pleiotropic and diverse [17, 20]. In particular, the interaction between NK and γδT cells in the context of immunological challenge has only recently undergone appraisal [103]. Reconstituting innate repertoires will provide unique possibilities to further elucidate these interactions.…”

Section: 4 Concluding Remarksmentioning

confidence: 99%

NK Cells and γδT Cells for Relapse Protection after Allogeneic Hematopoietic Cell Transplantation (HCT)

2017

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Purpose of review The outcome of allogeneic stem cell transplantation (allo-HCT) is still compromised by relapse and complications. NK cells and γδT cells, effectors which both function through MHC-unrestricted mechanisms, can target transformed and infected cells without inducing Graft-versus-Host Disease (GVHD). Allo-HCT platforms based on CD34+ selection or αβ-TCR depletion result in low grades of GVHD, early immune reconstitution (IR) of NK and γδT cells and minimal usage of GVHD prophylaxis. In this review we will discuss strategies to retain and expand the quantity, diversity and functionality of these reconstituting innate cell types. Recent findings Bisphosphonates, IL-15 cytokine administration, specific antibodies, checkpoint inhibitors and (CMV based) vaccination are currently being evaluated to enhance IR. All these approaches have shown to potentially enhance both NK and γδT cell immuno-repertoires. Summary Rapidly accumulating data linking innate biology to proposed clinical immune interventions, will give unique opportunities to unravel shared pathways which determine the Graft-versus-Tumor effects of NK and γδT cells.

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Human γδ T‐cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation

et al. 2019

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Background Although γδ T cells comprise up to 10% of human peripheral blood T cells, questions remain regarding their role in disease states and T‐cell receptor (TCR) clonal expansions. We dissected anti‐viral functions of human γδ T cells towards influenza viruses and defined influenza‐reactive γδ TCRs in the context of γδ‐TCRs across the human lifespan. Methods We performed 51Cr‐killing assay and single‐cell time‐lapse live video microscopy to define mechanisms underlying γδ T‐cell‐mediated killing of influenza‐infected targets. We assessed cytotoxic profiles of γδ T cells in influenza‐infected patients and IFN‐γ production towards influenza‐infected lung epithelial cells. Using single‐cell RT‐PCR, we characterised paired TCRγδ clonotypes for influenza‐reactive γδ T cells in comparison with TCRs from healthy neonates, adults, elderly donors and tissues. Results We provide the first visual evidence of γδ T‐cell‐mediated killing of influenza‐infected targets and show distinct features to those reported for CD8+ T cells. γδ T cells displayed poly‐cytotoxic profiles in influenza‐infected patients and produced IFN‐γ towards influenza‐infected cells. These IFN‐γ‐producing γδ T cells were skewed towards the γ9δ2 TCRs, particularly expressing the public GV9‐TCRγ, capable of pairing with numerous TCR‐δ chains, suggesting their significant role in γδ T‐cell immunity. Neonatal γδ T cells displayed extensive non‐overlapping TCRγδ repertoires, while adults had enriched γ9δ2‐pairings with diverse CDR3γδ regions. Conversely, the elderly showed distinct γδ‐pairings characterised by large clonal expansions, a profile also prominent in adult tissues. Conclusion Human TCRγδ repertoire is shaped by age, tissue compartmentalisation and the individual's history of infection, suggesting that these somewhat enigmatic γδ T cells indeed respond to antigen challenge.

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Two alternate strategies for innate immunity to Epstein-Barr virus: One using NK cells and the other NK cells and γδ T cells

Abstract: Djaoud et al. show that Epstein–Barr virus infection triggers two types of human innate immune response, one mediated by the combination of NK cells and γδ T cells and the other committed to a strong NK cell response with little involvement of γδ T cells.

Cited by 61 publications

References 51 publications

Diversification of human NK cells: Lessons from deep profiling

Diversification of human NK cells: Lessons from deep profiling

NK Cells and γδT Cells for Relapse Protection after Allogeneic Hematopoietic Cell Transplantation (HCT)

Human γδ T‐cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation

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