T cell–dependent production of IFN-γ by NK cells in response to influenza A virus

He, Xiao; Draghi, Monia; Mahmood, Kutubuddin; Holmes, Tyson H.; Kemble, George; Dekker, Cornelia L.; Arvin, Ann M.; Parham, Peter; Greenberg, Harry B.

doi:10.1172/jci22797

Cited by 139 publications

(108 citation statements)

References 58 publications

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“…Our study extends the results of previous publications that used similar in vitro infection systems (38,47 (47). This may be explained, at least in part, by differences in IAV-specific memory T cell responses, because T cells were not depleted in the latter study and T cell-derived IL-2 was clearly shown to enhance NK cell responses.…”

Section: Discussionsupporting

confidence: 87%

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

Ahlenstiel¹,

Martin²,

Gao³

et al. 2008

J. Clin. Invest.

120

145

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Section: Discussionsupporting

confidence: 87%

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

Ahlenstiel¹,

Martin²,

Gao³

et al. 2008

J. Clin. Invest.

120

145

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“…To assess NK-and T-cell functional responses to influenza-virus infection, we modified an assay previously described by He et al and Long et al (33,35,36). PBMCs were incubated with influenza virus, resulting in infection of 60-70% of monocytes (Fig.…”

Section: Robust Inflammatory Responses To Influenza a Virus In Pregnamentioning

confidence: 99%

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Kay¹,

Fukuyama²,

Aziz

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. Although some data suggest that natural killer (NK)-and T-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. Thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (IIV), 7 d after vaccination, and 6 wk postpartum. Expression of CD107a (a marker of cytolysis) and production of IFN-γ and macrophage inflammatory protein (MIP) 1β were assessed by flow cytometry. Pregnant women had a significantly increased percentage of NK cells producing a MIP-1β response to pH1N1 virus compared with nonpregnant women pre-IIV [median, 6.66 vs. 0.90% (P = 0.0149)] and 7 d post-IIV [median, 11.23 vs. 2.81% (P = 0.004)], indicating a heightened chemokine response in pregnant women that was further enhanced by the vaccination. Pregnant women also exhibited significantly increased T-cell production of MIP-1β and polyfunctionality in NK and T cells to pH1N1 virus pre-and post-IIV. NK-and T-cell polyfunctionality was also enhanced in pregnant women in response to the H3N2 viral strain. In contrast, pregnant women had significantly reduced NK-and T-cell responses to phorbol 12-myristate 13-acetate and ionomycin. This type of stimulation led to the conclusion that NK-and T-cell responses during pregnancy are suppressed, but clearly this conclusion is not correct relative to the more biologically relevant assays described here. Robust cellular immune responses to influenza during pregnancy could drive pulmonary inflammation, explaining increased morbidity and mortality.

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“…21 In addition, evidence emerged that NK cell-mediated immune responses also benefit from CD4 C T cell help. 9,[22][23][24][25][26][27][28] In certain infectious disease and tumor models, the cross-talk between CD4…”

Section: Introductionmentioning

confidence: 99%

“…9,[22][23][24][25][26][27][28] Regulatory T cells were reported to restrain IL-2 dependent CD4 C T cell help for NK cell proliferation and activity. [29][30][31] Our previous study demonstrated that adoptive transfer of IL-12/15/18-pretreated NK cells into irradiated tumor-bearing mice resulted in antitumor activity that required the presence of host CD4 C T cells and IL-2.…”

Section: Introductionmentioning

confidence: 99%

Adoptively transferred natural killer cells maintain long-term antitumor activity by epigenetic imprinting and CD4⁺T cell help

Hölsken

Miller

et al. 2016

OncoImmunology

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Natural killer (NK) cell infusions can induce remissions in subsets of patients with different types of cancer. The optimal strategies for NK cell activation prior to infusion are still under debate. There is recent evidence that NK cells can acquire long-term functional competence by preactivation with the cytokines IL-12/15/18. The mechanisms supporting the maintenance of long-term NK cell antitumor activity are incompletely understood. Here, we show that NK cells preactivated in vitro with IL-12/15/18, but not with IL-15 alone, maintained high antitumor activity even 1 mo after transfer into lymphopenic RAG-2The NK cell intrinsic ability for IFNg production coincided with demethylation of the conserved non-coding sequence (CNS) 1 in the Ifng locus, previously shown to enhance transcription of Ifng. In a xenograft melanoma mouse model, human IL-12/15/18-preactivated NK cells rejected tumors more efficiently. In RAG-2C T cells further improved the long-term competence of NK cells for IFNg production that was dependent on IL-2. CD4C T cell activation during homeostatic proliferation required macrophages and further promoted the long-term NK cell antitumor activity. Thus, NK cells can "remember" a previous exposure to cytokines by epigenetic imprinting resulting in a remarkable stability of the IFNg-producing phenotype after adoptive transfer. In addition, our results support combination of cytokine-preactivated NK cells with CD4 C T cell activation upon lymphopenic conditioning to achieve long-term NK cell effector function for cancer immunotherapy.

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T cell–dependent production of IFN-γ by NK cells in response to influenza A virus

Cited by 139 publications

References 58 publications

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Adoptively transferred natural killer cells maintain long-term antitumor activity by epigenetic imprinting and CD4⁺T cell help

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T cell–dependent production of IFN-γ by NK cells in response to influenza A virus

Cited by 139 publications

References 58 publications

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Adoptively transferred natural killer cells maintain long-term antitumor activity by epigenetic imprinting and CD4+T cell help

Contact Info

Product

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Adoptively transferred natural killer cells maintain long-term antitumor activity by epigenetic imprinting and CD4⁺T cell help