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            T-Cell Help Enhances NK Cell Function following Therapeutic HIV-1 Vaccination

Jost, Stéphanie; Tomezsko, Phillip; Rands, Keith; Tóth, Ildikó; Lichterfeld, Mathias; Gandhi, Rajesh T.; Altfeld, Marcus

doi:10.1128/jvi.00924-14

Cited by 55 publications

(48 citation statements)

References 34 publications

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“…This could efficiently prevent virus replication and dissemination in the host. Enhanced NK cell activity induced by cellular immunity was also shown after rabies virus, Plasmodium falciparum, and HIV vaccination (40)(41)(42). In these studies, IL-2 from reexposed CD4 ϩ T cells again played a key role in enhancement of NK cell responses.…”

Section: Discussionmentioning

confidence: 71%

Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages

Wu¹,

Frascaroli²,

Bayer³

et al. 2015

J Virol

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Control of human cytomegalovirus (HCMV) requires a continuous immune surveillance, thus HCMV is the most important viral pathogen in severely immunocompromised individuals. Both innate and adaptive immunity contribute to the control of HCMV. Here, we report that peripheral blood natural killer cells (PBNKs) from HCMV-seropositive donors showed an enhanced activity toward HCMV-infected autologous macrophages. However, this enhanced response was abolished when purified NK cells were applied as effectors. We demonstrate that this enhanced PBNK activity was dependent on the interleukin-2 (IL-2) secretion of CD4 ؉ T cells when reexposed to the virus. Purified T cells enhanced the activity of purified NK cells in response to HCMV-infected macrophages. This effect could be suppressed by IL-2 blocking. Our findings not only extend the knowledge on the immune surveillance in HCMV-namely, that NK cell-mediated innate immunity can be enhanced by a preexisting T cell antiviral immunity-but also indicate a potential clinical implication for patients at risk for severe HCMV manifestations due to immunosuppressive drugs, which mainly suppress IL-2 production and T cell responsiveness. IMPORTANCE Human cytomegalovirus (HCMV) is never cleared by the host after primary infection but instead establishes a lifelong latent infection with possible reactivations when the host=s immunity becomes suppressed. Both innate immunity and adaptive immunity are important for the control of viral infections. Natural killer (NK) cells are main innate effectors providing a rapid response to virus-infected cells. Virus-specific T cells are the main adaptive effectors that are critical for the control of the latent infection and limitation of reinfection. In this study, we found that IL-2 secreted by adaptive CD4 ؉ T cells after reexposure to HCMV enhances the activity of NK cells in response to HCMV-infected target cells. This is the first direct evidence that the adaptive T cells can help NK cells to act against HCMV infection.H uman cytomegalovirus (HCMV) infects and establishes a persistent infection in the majority of humans worldwide. Postnatally it rarely causes severe complications in healthy individuals. However, HCMV is a significant cause of morbidity and mortality in severely immunocompromised individuals (1). This indicates the importance of immune surveillance in the control of HCMV. While T cells and HCMV antibodies are considered to be the main effectors of protective immunity, recent evidence supports the idea that NK cells also play an important role in the control of HCMV (2-4) and that NK cells degranulate after contact with HCMV-infected cells (5, 6). We have shown before that humoral antiviral immunity enhanced the degranulation and gamma interferon (IFN-␥) production of NK cells in response to HCMV-infected macrophages (6). In this article, we show that NK cell activity can also be enhanced by the T cell-mediated antiviral immunity against HCMV.The activity of NK cells is regulated by (i) a balance of signals from act...

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Section: Discussionmentioning

confidence: 71%

Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages

Wu¹,

Frascaroli²,

Bayer³

et al. 2015

J Virol

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“…PAMP‐containing adjuvants are typically required to improve the immunogenicity of subunit or vectored vaccines, which lack these ligands. Several studies have documented enhancement of NK cell activation by adjuvants . IL‐15‐matured DCs exposed in vitro to the TLR‐4 agonist AS04‐adjuvanted human papilloma virus (HPV) VLP vaccine can potentiate NK cell activation and killing of HPV‐infected cells compared to either IL‐4‐matured DCs or VLP alone; this effect was attributed to the superior cytokine‐producing ability of the DCs .…”

Section: The Role Of Vaccine Adjuvants In Promoting Nk Cell Responsesmentioning

confidence: 99%

“…In vitro cytokine activation with IL‐18 and IL‐12 and/or IL‐15 induces expression of CD25, thereby generating CIML NK cells with enhanced responsiveness (demonstrated by IFN‐γ production and cytotoxicity) to picomolar concentrations of IL‐2 . More importantly perhaps, CIML NK cells can be induced by vaccination in response to CD4 + T cell‐derived IL‐2 and myeloid cell‐derived IL‐12 and type I interferons, and have been implicated in the enhancement of NK cell function ex vivo . Vaccination‐induced CIML NK cells can be detected for up to 12 weeks postvaccination in European subjects and up to 6 months in west African vaccines .…”

Section: Introductionmentioning

confidence: 99%

Vaccinating for natural killer cell effector functions

et al. 2018

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Vaccination has proved to be highly effective in reducing global mortality and eliminating infectious diseases. Building on this success will depend on the development of new and improved vaccines, new methods to determine efficacy and optimum dosing and new or refined adjuvant systems. NK cells are innate lymphoid cells that respond rapidly during primary infection but also have adaptive characteristics enabling them to integrate innate and acquired immune responses. NK cells are activated after vaccination against pathogens including influenza, yellow fever and tuberculosis, and their subsequent maturation, proliferation and effector function is dependent on myeloid accessory cell‐derived cytokines such as IL‐12, IL‐18 and type I interferons. Activation of antigen‐presenting cells by live attenuated or whole inactivated vaccines, or by the use of adjuvants, leads to enhanced and sustained NK cell activity, which in turn contributes to T cell recruitment and memory cell formation. This review explores the role of cytokine‐activated NK cells as vaccine‐induced effector cells and in recall responses and their potential contribution to vaccine and adjuvant development.

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“…Similarly, it has been shown that the response of T cells induced by a HIV-1 specific vaccine is able to improve NK cell function, typically impaired in individuals with HIV-1 chronic infection [91]. However, vaccination against specific viral antigens (influenza, vesicular stomatitis virus, or HIV-1) has been shown to generate not only long-lived cytokine-activated NK cells but also memory-like NK cells capable of protecting mice against viral challenge in a virus/antigen-specific manner [47].…”

Section: Antigen-independent Long-lived Cytokine-activated Nk Cellmentioning

confidence: 99%

The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

Gabrielli

Ortolani

Zotto

et al. 2016

Journal of Immunology Research

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CD4 ⁺ T-Cell Help Enhances NK Cell Function following Therapeutic HIV-1 Vaccination

Cited by 55 publications

References 34 publications

Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages

Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages

Vaccinating for natural killer cell effector functions

The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

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CD4 + T-Cell Help Enhances NK Cell Function following Therapeutic HIV-1 Vaccination

Cited by 55 publications

References 34 publications

Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages

Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages

Vaccinating for natural killer cell effector functions

The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

Contact Info

Product

Resources

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CD4 ⁺ T-Cell Help Enhances NK Cell Function following Therapeutic HIV-1 Vaccination