Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses

Díaz-Salazar, Carlos; Sun, Joseph C.

doi:10.1016/j.celrep.2020.108186

Cited by 4 publications

(1 citation statement)

References 45 publications

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“…Studies in mice presented by Dr Joseph Sun showed that the activating receptor Ly49H is expressed on NK cells and binds with high specificity to the mouse cytomegalovirus (MCMV)-encoded glycoprotein m157, which is expressed on infected cells to drive the expansion of virus-specific NK cells during the acute phase of MCMV infection. This proliferation of NK cells depended on the presence of CD8 + T cells 18 . The dependence of NK cell expansion and memory on adaptive immune cells points to another potential pathway for exploring SVEs -namely the potential effect of live vaccines, which are known to initiate adaptive immune responses, on NK cell memory and function.…”

Section: Indications For Sves Within Innate Immunitymentioning

confidence: 94%

NIAID workshop on secondary vaccine effects

Joffe¹,

Park²,

Augustine³

et al. 2021

Nat Immunol

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Section: Indications For Sves Within Innate Immunitymentioning

confidence: 94%

NIAID workshop on secondary vaccine effects

Joffe¹,

Park²,

Augustine³

et al. 2021

Nat Immunol

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NK- and T-cell repertoire is established early after allogeneic HSCT and is imprinted by CMV reactivation

Schäfer,

Calderin Sollet,

Hervé

et al. 2024

Blood Advances

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Besides genetic influences, non-genetic factors such as graft-versus-host disease (GvHD) and viral infections have been shown as important shapers of the immune reconstitution and diversification processes after hematopoietic stem cell transplantation (HSCT). However, the differential susceptibility to immune modulation by non-genetic factors is not fully understood. We determined to follow the reconstitution of the T cell receptor (TCR) repertoire through immune-sequencing, of natural killer (NK) cells using a 35-marker spectral flow cytometry panel, and in relation to clinical events. Longitudinal investigation was performed on samples derived from 54 HSCT recipients during the first-year post-HSCT. We confirmed a significant contraction in TCR repertoire diversity with a remarkable stability over time. CMV reactivation had the ability to significantly change TCR repertoire clonality and composition, with a long-lasting imprint. Our data further revealed skewing of NK cell reconstitution in CMV reactivated recipients, with an increased frequency of KIR2DL2L3S2+ adaptive, cytolytic and functional CD107a+ NK cells concomitant with a reduced pool of NKG2A+ NK cells. We provided support that CMV might act as one of the more important driver of peripheral homeostatic proliferation of circulating specific T and NK cells, which can be viewed as a compensatory mechanism to establish a new peripheral repertoire.

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Decitabine Treatment Induces a Viral Mimicry Response in Cervical Cancer Cells and Further Sensitizes Cells to Chemotherapy

Alexandraki¹,

Strati²

2022

IJMS

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Purpose: To investigate the anti-cancer, chemosensitizing and/or immunomodulating effects of decitabine (DAC) to be used as a potential therapeutic agent for the treatment of cervical cancer (CC). Methods: Cervical cancer cell lines were treated with low doses of DAC treatment used as a single agent or in combination with chemotherapy. End-point in vitro assays were developed as indicators of the anti-cancer and/or immunomodulating effects of DAC treatment in CC cells. These assays include cell viability, cell cycle analysis, apoptosis, induction of a viral-mimicry response pathway, expression of MHC-class I and PD-L1 and chemosensitivity. Results: High and low doses of DAC treatment induced reduction in cell viability in HeLa (HPV18+), CaSki (HPV16+) and C33A (HPV−) cells. Specifically, a time-dependent reduction in cell viability of HeLa and CaSki cells was observed accompanied by robust cell cycle arrest at G2/M phase and alterations in the cell cycle distribution. Decrease in cell viability was also observed in a non-transformed immortal keratinocyte (HaCat) suggesting a non-cancer specific target effect. DAC treatment also triggered a viral mimicry response through long-term induction of cytoplasmic double-stranded RNA (dsRNA) and activation of downstream IFN-related genes in both HPV+ and HPV− cells. In addition, DAC treatment increased the number of CC cells expressing MHC-class I and PD-L1. Furthermore, DAC significantly increased the proportion of early and late apoptotic CC cells quantified using FACS. Our combination treatments showed that low dose DAC treatment sensitizes cells to chemotherapy. Conclusions: Low doses of DAC treatment promotes robust induction of a viral mimicry response, immunomodulating and chemosensitizing effects in CC, indicating its promising therapeutic role in CC in vitro.

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Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses

Cited by 4 publications

References 45 publications

NIAID workshop on secondary vaccine effects

NIAID workshop on secondary vaccine effects

NK- and T-cell repertoire is established early after allogeneic HSCT and is imprinted by CMV reactivation

Decitabine Treatment Induces a Viral Mimicry Response in Cervical Cancer Cells and Further Sensitizes Cells to Chemotherapy

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