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Differential alteration of CD56bright and CD56dim natural killer cells in frequency, phenotype, and cytokine response in chronic hepatitis C virus infection

  • Original Article—Liver, Pancreas, and Biliary Tract
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Abstract

Background

Natural killer (NK) cells play an important role in immune responses to virus infection. The cell population consists of CD56bright (bright-subset) and CD56dim (dim-subset) subsets that possess armed functions of cytokine production and cytolysis, respectively. How these subsets are involved in chronic hepatitis C virus infection (CHC) remains obscure.

Methods

We investigated the frequency, phenotype, and cytokine response of these subsets in blood from CHC patients and healthy subjects (HS).

Results

Dim-subset, but not bright-subset, showed lower frequency in the patients than in HS. Bright-subset from the patients more frequently expressed the NKG2A/CD94 inhibitory receptor than that from HS, while both subsets from the patients expressed lower levels of the NKG2D activating receptor. Both subsets from the patients displayed a significantly higher level of the signal transducer and activator of transcription (STAT) 1, compared with the HS. Upon stimulation with interferon-α, bright-subset activated less STAT4, required for interferon-γ production, and dim-subset activated more STAT1, required for cytolysis, in the patients than in HS.

Conclusions

These results indicate alterations of NK cell subsets in frequency, phenotype, and cytokine response in CHC, which might be associated with the immune pathogenesis of CHC.

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Abbreviations

NK:

Natural killer

IFN:

Interferon

IL:

Interleukin

HCV:

Hepatitis C virus

CHC:

Chronic hepatitis C virus infection

CHB:

Chronic hepatitis B virus infection

PBMC:

Peripheral blood mononuclear cell

STAT:

Signal transducer and activator of transcription

pSTAT:

Phosphorylated-signal transducer and activator of transcription

HS:

Healthy subjects

ISG:

Interferon-stimulated gene

MICA:

Major histocompatibility complex class I-related chain A

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Acknowledgments

This work was supported by Grants-in-aid for Scientific Research (to T. Takehara and T. Miyagi) and by a grant for the Global Centers of Excellence Program (to T. Miyagi) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a Grant-in-aid (to T. Takehara) from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Takuya Miyagi, Satoshi Shimizu, Tomohide Tatsumi, Kumiko Nishio, Naoki Hiramatsu, Tatsuya Kanto & Tetsuo Takehara

  2. Global Centers of Excellence Program, Frontier Biomedical Science Underlying Organelle Network Biology, Osaka University, Suita, Osaka, Japan

    Takuya Miyagi & Tetsuo Takehara

  3. Kansai-Rosai Hospital, Amagasaki, Hyogo, Japan

    Norio Hayashi

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  1. Takuya Miyagi
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Correspondence to Tetsuo Takehara.

Additional information

T. Miyagi and S. Shimizu contributed equally to this work and share the first authorship.

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Miyagi, T., Shimizu, S., Tatsumi, T. et al. Differential alteration of CD56bright and CD56dim natural killer cells in frequency, phenotype, and cytokine response in chronic hepatitis C virus infection. J Gastroenterol 46, 1020–1030 (2011). https://doi.org/10.1007/s00535-011-0408-8

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