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Induction of hepatitis B virus specific T cell responses by activating innate immune response

Research Project

Project/Area Number 26461015
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionNagoya City University

Principal Investigator

ISOGAWA Masanori  名古屋市立大学, 大学院医学研究科, 助教 (50723201)

Co-Investigator(Renkei-kenkyūsha) Tanaka Yasuhito  名古屋市立大学, 大学院医学研究科, 教授 (90336694)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsB型肝炎ウイルス / HBV特異的CD8+T細胞 / 抗原提示 / 活性化樹状細胞
Outline of Final Research Achievements

In this study, we determined whether endogenous antigen presentation by hepatocytes or cross-presentation by bone marrow derived cells is more important in the induction of hepatitis B virus (HBV)-specific T cell responses. To do so, we employed transgenic mice that replicate HBV at high level in the liver (HBV-Tg mice) to generate HBV-Tg mice whose MHC class I expression is absent on bone marrow derived cells, or parenchymal cells. We then adoptively transferred HBV-specific T cells, and monitored their responsiveness. Our data suggest that cross-presentation by hematopoietic cells is required for the optimum expansion of HBV-specific T cells, but endogenous antigen presentation by non-hematopoietic cells, presumably hepatocytes, is far more essential in the expansion and cytolytic differentiation of HBV-specific T cells.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (36 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (27 results) (of which Int'l Joint Research: 14 results)

  • [Journal Article] Molecular epidemiology of co-infection with hepatitis B virus and human immunodeficiency virus (HIV) among adult patients in Harare, Zimbabwe2017

    • Author(s)
      Baudi I, Iijima S, Chin'ombe N, Mtapuri-Zinyowera S, Murakami S, Isogawa M, Hachiya A, Iwatani Y, and Tanaka Y
    • Journal Title

      Journal of Medical Virology

      Volume: 89 Issue: 2 Pages: 257-266

    • DOI

      10.1002/jmv.24641

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A new class of hepatitis B and D virus entry inhibitors, proanthocyanidin and its analogs, that directly act on the viral large surface proteins.2017

    • Author(s)
      Tsukuda S, Watashi K, Hojima T, Isogawa M, Iwamoto M, Omagari K, Suzuki R, Aizaki H, Kojima S, Sugiyama M, Saito A, Tanaka Y, Mizokami M, Sureau C, Wakita T
    • Journal Title

      Hepatology

      Volume: 65 Issue: 4 Pages: 1104-1116

    • DOI

      10.1002/hep.28952

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] B型肝炎治療不応例における新規Entecavir耐性変異(rtA186T)の同定.2016

    • Author(s)
      林佐奈衣, 村上周子, 尾曲克己, 松居剛志, 飯尾悦子, 五十川正記, 渡邊綱正, 狩野吉康, 田中靖人.
    • Journal Title

      NAGOYA MEDICAL JOURNAL(名古屋市立大学医学会雑誌)

      Volume: 55(1) Pages: 35-42

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 新規核酸アナログ4'-C-cyano-2-amino-2'-deoxyadenosine、4'-C-cyano-2'-deoxyguanosineは薬剤耐性B型肝炎ウイルス変異株に対して有効である.2016

    • Author(s)
      林佐奈衣, 高松悠樹, 前田賢次, 村上周子, 尾曲克己, 松居剛志, 五十川正記, 渡邊綱正, 狩野吉康, 向後悟, 満屋裕明, 田中靖人.
    • Journal Title

      肝臓

      Volume: 57(6) Pages: 299-301

    • NAID

      130005160949

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Host genetic variants influencing the clinical course of Hepatitis B virus infection.2016

    • Author(s)
      Matsuura K, Isogawa M, Tanaka Y.
    • Journal Title

      J Med Virol.

      Volume: 88(3) Issue: 3 Pages: 371-9

    • DOI

      10.1002/jmv.24350

    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Journal Article] Host-virus interactions in hepatitis B virus infection.2015

    • Author(s)
      Guidotti LG, Isogawa M, Chisari FV.
    • Journal Title

      Curr Opin Immunol.

      Volume: 36 Pages: 61-6

    • DOI

      10.1016/j.coi.2015.06.016

    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Journal Article] Immunosurveillance of the liver by intravascular effector CD8(+) T cells.2015

    • Author(s)
      Guidotti LG, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L, Fiocchi A, Vacca M, Aiolfi R, Sammicheli S, Mainetti M, Cataudella T, Raimondi A, Gonzalez-Aseguinolaza G, Protzer U, Ruggeri ZM, Chisari FV, Isogawa M, Sitia G, Iannacone M.
    • Journal Title

      Cell

      Volume: 161(3) Issue: 3 Pages: 486-500

    • DOI

      10.1016/j.cell.2015.03.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Characterization of novel entecavir resistance mutations.2015

    • Author(s)
      Hayashi S, Murakami S, Omagari K, Matsui T, Iio E, Isogawa M, Watanabe T, Karino Y, Tanaka Y.
    • Journal Title

      J Hepatol.

      Volume: 63(3) Issue: 3 Pages: 546-53

    • DOI

      10.1016/j.jhep.2015.03.020

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Immunobiology of hepatitis B virus infection.2015

    • Author(s)
      Isogawa M, Tanaka Y.
    • Journal Title

      Hepatology Research

      Volume: 45 Issue: 2 Pages: 179-189

    • DOI

      10.1111/hepr.12439

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Hepatocellular carcinoma-associated core N51H mutation with BCP PC mutations in HBV genotype F1b enhances infectivity and up-regulates C-Myc and GAB22016

    • Author(s)
      Hayashi S, Khan AA, Ogawa K, Kawashima K, Simons-Petrusa B, Homan CE, McMahon BJ, Murakami S, Iijima S, Isogawa M, Watanabe T, Tanaka Y
    • Organizer
      The 67th Annual Meeting of the American Association for the Study of Liver Diseases(AASLD2016)
    • Place of Presentation
      John B. Hynes Veterans Memorial Convention Center, The United States of America, Boston,
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Silencing hepatitis B virus (HBV) gene expression in the liver by RNAi prevents HBV-specific CD8 T cell exhaustion2016

    • Author(s)
      Kawashima K, Isogawa M, Saito S, Tanaka Y
    • Organizer
      The 67th Annual Meeting of the American Association for the Study of Liver Diseases(AASLD2016)
    • Place of Presentation
      John B. Hynes Veterans Memorial Convention Center, The United States of America, Boston,
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The hepatitis B virus (HBV) core antigen expression level determines the rate of CD8 T cell mediated viral clearance2016

    • Author(s)
      Isogawa M, Kawashima K, Tsutsumi S, Tanaka Y
    • Organizer
      The 67th Annual Meeting of the American Association for the Study of Liver Diseases(AASLD2016)
    • Place of Presentation
      John B. Hynes Veterans Memorial Convention Center, The United States of America, Boston,
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hepatitis B virus (HBV) antigen suppression prevents HBV-specific CD8 T cell exhaustion2016

    • Author(s)
      Kawashima K, Isogawa M, Saito S, Nakajima A, Tanaka Y
    • Organizer
      Asian Pacific Digestive Week 2016 (APDW 2016)
    • Place of Presentation
      Kobe Convention Center (International Exhibition Center), Hyogo, Kobe
    • Year and Date
      2016-11-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel 4'-modified nucleoside analogs,CAdA and CdG,strongly suppress the replication of wild-type hepatitis B virus and drug-resistant mutants2016

    • Author(s)
      Hayashi S, Takamatsu Y, Maeda K, Murakami S, Omagari K, Matsui T, Isogawa M, Watanabe T, Karino Y, Kohgo S, Mitsuya H, Tanaka Y
    • Organizer
      2016 International HBV Meeting on the Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Centennial Concert Hall, Yonsei University, Korea, Seoul
    • Year and Date
      2016-09-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Proanthocyanidin and its analogs are new class of HBV and HDV entry inhibitors that target the viral preS1 region2016

    • Author(s)
      Tsukuda S, Watashi K, Hojima T, Isogawa M, Iwamoto M, Suzki R, Aizaki H, Kojima S, Sugiyama M, Saito A, Tanaka Y, Mizokami M, Wakita T
    • Organizer
      2016 International HBV Meeting on the Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Centennial Concert Hall, Yonsei University, Korea, Seoul
    • Year and Date
      2016-09-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Retinoic acid inducible gene-I like receptors (RLRs) stimulation suppresses hepatitis B virusn (HBV) replication and induces cytotolytic ability of HBV-specific CD8 T cells more efficiently than Toll like receptor 3 stimulation2016

    • Author(s)
      Kawashima K, Isogawa M, Tanaka Y
    • Organizer
      2016 International HBV Meeting on the Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Centennial Concert Hall, Yonsei University, Korea, Seoul
    • Year and Date
      2016-09-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Suppression of the hepatitis B virus (HBV) antigen expression in the liver prevents HBV-specific CD8 T cell exhaustion2016

    • Author(s)
      Kawashima K, Isogawa M, Saito S, Nakajima A, Tanaka Y
    • Organizer
      2016 International HBV Meeting on the Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Centennial Concert Hall, Yonsei University, Korea, Seoul
    • Year and Date
      2016-09-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] B型肝炎ウイルス(HBV)抗原抑制による機能的なHBV特異的CD8+T細胞応答の誘導2016

    • Author(s)
      五十川正記, 河島圭吾, 田中靖人
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ幕張, 千葉,千葉
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 異なるHBV遺伝子型によるHBV抗原遷延化率の違い~肝臓内CD8+T細胞応答およびコア抗原発現量の相関性2016

    • Author(s)
      河島圭吾, 五十川正記, 堤進, 村上周子, 斉藤聡, 中島淳, 田中靖人
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      東京ベイ幕張ホール, 千葉,千葉
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肝臓内HBV抗原抑制によるHBV特異的エフェクターCD8+T細胞応答の誘導2016

    • Author(s)
      河島圭吾, 五十川正記, 田中靖人
    • Organizer
      第102回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル, 東京, 新宿
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Endogenous antigen presentation by hepatocytes plays an essential role in the induction of HBV-specific CD8+ T cell responses2016

    • Author(s)
      Isogawa M, Murata Y, Kawashima K, Tanaka Y
    • Organizer
      4th Taiwan-Korea-Japan Research Symposium on Hepatitis B Virus
    • Place of Presentation
      Academia Sinica, Taiwan, Taipei
    • Year and Date
      2016-04-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] Novel 4'-modified nucleoside analogs exert antiviral replication against hepatitis B virus with drug resistance mutations2016

    • Author(s)
      Hayashi S, Takamatsu Y, Maeda K, Murakami S, Omagari K, Matsui T, Isogawa M, Watanabe T, Karino Y, Kohgo S, Mitsuya H, Tanaka Y
    • Organizer
      25th Conference of the Asian Pasific Association for the Study of the Liver (APASL2016)
    • Place of Presentation
      International Convention Center Pamir, Tokyo, Japan
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Host and viral determinants for differential hepatitis B virus clearance between genotypes2016

    • Author(s)
      Kawashima K, Isogawa M, Tsutsumi S, Murakami S, Saito S, Nakajima A, Tanaka Y. 25th Conference of the Asian Pasific Association for the Study of the Liver (APASL2016), 2016/2/
    • Organizer
      25th Conference of the Asian Pasific Association for the Study of the Liver (APASL2016)
    • Place of Presentation
      International Convention Center Pamir, Tokyo, Japan
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clearance rate of hepatitis B virus differs between genotypes in association with CD8+ T cell activation in the liver.2015

    • Author(s)
      Isogawa M, Kawashima K, Tsutsumi S, Murakami S, Tanaka Y
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡国際会議場、福岡
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Identification of a flavonoid derivative that directly acts on hepatitis B virus surface protein and inhibits viral entry.2015

    • Author(s)
      Tsukuda S, Watashi K, Hamada Y, Isogawa M, Iwamoto M, Suzuki R, Aizaki H, Kojima S, Sugiyama M, Saito A, Tanaka Y, Mizokami M, Wakita T
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡国際会議場、福岡
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Endogenous antigen presentation by hepatocytes plays an essential role in the induction of HBV-specific CD8+ T cell responses2015

    • Author(s)
      Isogawa M, Murata Y, Kawashima K, Tanaka Y
    • Organizer
      The 66th Annual Meeting of the American Association for the Study of Liver Diseases(AASLD2015)
    • Place of Presentation
      Moscone West Convention Center, San Francisco, USA
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hepatocellular carcinoma-associated core N51H mutation enhances infectivity of hepatitis B virus genotype F1b by facilitating dimerization of the core protein2015

    • Author(s)
      Hayashi S, Khan A, Ogawa K, Kawashima K, Simons B, Jones C, Homan C, McMahon B, Murakami S, Iijima S, Isogawa M, Watanabe T, Tanaka Y
    • Organizer
      2015 International Meeting on the Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Dolce Bad Nauheim, Germany
    • Year and Date
      2015-10-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Differential hepatitis B virus clearance between genotypes is correlated with HBV-specific CD8+T cell responses in the liver2015

    • Author(s)
      Kawashima K, Isogawa M, Tsutsumi S, Murakami S, Saito S, Nakajima A, Tanaka Y
    • Organizer
      2015 International Meeting on the Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Dolce Bad Nauheim, Germany
    • Year and Date
      2015-10-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparison of cytopathic and non-cytopathic antiviral effects of interferon alpha and lambda against hepatitis B virus infection.2015

    • Author(s)
      Tsutsumi S, Watanabe T, Kawashima K, Murakami S, Isogawa M, Tanaka Y
    • Organizer
      2015 International Meeting on the Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Dolce Bad Nauheim, Germany
    • Year and Date
      2015-10-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規エンテカビル耐性株の同定とその特徴2015

    • Author(s)
      林佐奈衣, 村上周子, 尾曲克己, 松居剛志, 飯尾悦子, 五十川正記, 渡邊綱正, 狩野吉康, 田中靖人
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      ホテル日航熊本、熊本県
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 肝細胞による内因性抗原提示と樹状細胞による外因性抗原提示がHBV特異的CD8+T細胞応答に及ぼす相対的役割2015

    • Author(s)
      五十川正記, 村田泰洋, 田中靖人
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      ホテル日航熊本、熊本県
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 異なるHBV遺伝子型間で認められるHBV抗原遷延化率の違いと肝臓内CD8+T細胞応答の相関性2015

    • Author(s)
      河島圭吾, 五十川正記, 松波加代子, 堤進, 村上周子, 渡邊綱正, 斉藤聡, 中島淳, 田中靖人
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      ホテル日航熊本、熊本県
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] Check Point Inhibitors and Therapy for HBV Infection.2015

    • Author(s)
      Isogawa M.
    • Organizer
      17th International Conference on Emerging Infectious Diseases
    • Place of Presentation
      Taipei (Taiwan)
    • Year and Date
      2015-01-25
    • Related Report
      2014 Research-status Report
  • [Presentation] HBV 特異的 CD8+T 細胞の増殖と細胞傷害能は肝細胞による内因性抗原提示に依存する2014

    • Author(s)
      五十川 正記、村田 泰洋、田中 靖人
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県・横浜市)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Endogenous Antigen Presentation By Hepatocytes Plays and Essential Role in the Induction of HBV-Specific CD8+ T cell responses.2014

    • Author(s)
      Isogawa M, Murata Y, Sheikh K, Tanaka Y, Chisari FV.
    • Organizer
      2014 International Meeting on Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Los Angeles (USA)
    • Year and Date
      2014-09-03 – 2014-09-06
    • Related Report
      2014 Research-status Report
  • [Presentation] A VLP Based Therapeutic HBV Vaccine Designed to Inhibit Viral Spread.2014

    • Author(s)
      Whitacre D, Peterson D, Sureau C, Milich D, Isogawa M.
    • Organizer
      International Meeting on Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Los Angeles (USA)
    • Year and Date
      2014-09-03 – 2014-09-06
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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