The Role of Natural Killer Cells and CD8+ T Cells in Hepatitis B Virus Infection

Schuch, Anita; Hoh, Alexander; Thimme, Robert

doi:10.3389/fimmu.2014.00258

Cited by 74 publications

(58 citation statements)

References 107 publications

(137 reference statements)

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“…In addition, chimpanzees inoculated with ∼5 3 10 7 GE HBV DNA showed that noncytopathic antiviral mechanisms contributed to HBV clearance, possibly via NK cells (39), suggesting that high HBV doses might induce the noncytopathic antiviral mechanisms of NK cells mediating HBV clearance. Other studies, however, have indicated that high viral load may be associated with a reduction of noncytolytic NK cell responses (48,51). In our model, we show that the primary role of NK cells is to induce anti-HBV CD8 + T cell responses rather than to exert direct antiviral activity.…”

mentioning

confidence: 47%

NK Cells Help Induce Anti–Hepatitis B Virus CD8+ T Cell Immunity in Mice

Zheng¹,

Sun

Wei

et al. 2016

The Journal of Immunology

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Although recent clinical studies demonstrate that NK cell function is impaired in hepatitis B virus (HBV)–persistent patients, whether or how NK cells play a role in anti-HBV adaptive immunity remains to be explored. Using a mouse model mimicking acute HBV infection by hydrodynamic injection of an HBV plasmid, we observed that although serum hepatitis B surface Ag and hepatitis B envelope Ag were eliminated within 3 to 4 wk, HBV might persist for >8 wk in CD8−/− mice and that adoptive transfer of anti-HBV CD8+ T cells restored the ability to clear HBV in HBV-carrier Rag1−/− mice. These results indicate that CD8+ T cells are critical in HBV elimination. Furthermore, NK cells increased IFN-γ production after HBV plasmid injection, and NK cell depletion led to significantly increased HBV persistence along with reduced frequency of hepatitis B core Ag–specific CD8+ T cells. Adoptive transfer of IFN-γ–sufficient NK cells restored donor CD8+ T cell function, indicating that NK cells positively regulated CD8+ T cells via secreting IFN-γ. We also observed that NK cell depletion correlated with decreased effector memory CD8+ T cell frequencies. Importantly, adoptive transfer experiments showed that NK cells were involved in anti-HBV CD8+ T cell recall responses. Moreover, DX5+CD49a− conventional, but not DX5−CD49a+ liver-resident, NK cells were involved in improving CD8+ T cell responses against HBV. Overall, the current study reveals that NK cells, especially DX5+CD49a− conventional NK cells, promote the antiviral activity of CD8+ T cell responses via secreting IFN-γ in a mouse model mimicking acute HBV infection.

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mentioning

confidence: 47%

NK Cells Help Induce Anti–Hepatitis B Virus CD8+ T Cell Immunity in Mice

Zheng¹,

Sun

Wei

et al. 2016

The Journal of Immunology

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“…In contrast, CHB infection is characterized by an exhausted phenotype of specific T cells, possibly because of (i) strong and long‐term exposure to secreted HBV antigens (ie APC‐induced T‐cell suppression), (ii) overall lack of activation of innate immune cells and deficient antigen presentation by infected cells and (iii) a highly tolerogenic environment in the infected liver because of over representation of immune‐modulatory cells and secretion of tolerogenic molecules (Figure ) . Interestingly, it has also been shown that the function and cross‐talk of other cell types, including NK/NKT dendritic cells are impaired during CHB, contributing to the overall lack of efficient immune response against the virus …”

Section: Immune System Manipulationmentioning

confidence: 99%

Novel targets for hepatitis B virus therapy

Testoni

Durantel

Zoulim

2017

Liver International

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“…Many research groups have shown that NK cells in patients with chronic hepatitis B become defective in terms of producing IFN-c with preserved cytotoxic activity [31][32][33][34][35]. Furthermore, TRAIL (TNF-related apoptosis-inducing ligand)-expressing NK cells eliminate HBV-specific T cells which highly express the TRAIL death receptor TRAIL-R2 [36].…”

Section: Nk Cells and Dcs In Chronic Hbv Infectionmentioning

confidence: 99%

Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

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The Role of Natural Killer Cells and CD8+ T Cells in Hepatitis B Virus Infection

Cited by 74 publications

References 107 publications

NK Cells Help Induce Anti–Hepatitis B Virus CD8+ T Cell Immunity in Mice

NK Cells Help Induce Anti–Hepatitis B Virus CD8+ T Cell Immunity in Mice

Novel targets for hepatitis B virus therapy

Host–virus interactions in hepatitis B and hepatitis C infection

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