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Reproduction of virus-specific immunodeficiency in humanized mice

Research Project

Project/Area Number 25670198
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

FUJIWARA Shigeyoshi  独立行政法人国立成育医療研究センター, その他部局等, その他 (30173488)

Co-Investigator(Renkei-kenkyūsha) IMADOME Ken-ichi  国立成育医療研究センター, 母児感染研究部, 室長 (70392488)
MATSUDA Go  国立成育医療研究センター, 母児感染研究部, 研究員 (60392130)
KANEGANE Hirokazu  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (00293324)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsEBウイルス / ヒト化マウス / XIAP欠損症 / 免疫不全症 / サイトカイン / 血球貪食性リンパ組織球症
Outline of Final Research Achievements

To reproduce EBV-related immunodeficiency in humanized mice, hematopoietic stem cells were isolated from a patient with XIAP deficiency and transplanted to four NOG mice. Three of the four mice showed signs of reconstitution with human immune system components; 0.3-20.4% of PBMC was positive with human-specific anti-CD45 antibody. Two of the three mice were inoculated with EBV and EBV DNA (up to 8×10E+3 copies/μg DNA) was detected in the peripheral blood 6-10 weeks post inoculation. The percentage of CD8+ T cells among peripheral blood lymphocytes increased drastically to ~80% in these mice. These results indicated that humanized mice could be prepared with stem cells isolated from a patient with XIAP deficiency, and EBV can infect these mice and induce CD8+ T cell responses. Peripheral blood levels of human cytokines are currently evaluated to see if hypercytokinemia, characteristic to EBV infection in patients with XIAP deficiency, is reproduced in these mice.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (11 results)

All 2015 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Invited: 3 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Modeling EBV infection and pathogenesis in new-generation humanized mice2015

    • Author(s)
      Fujiwara S, Imadome K, and Takei M
    • Journal Title

      Exp Mol Med

      Volume: 47 Issue: 1 Pages: e135-e135

    • DOI

      10.1038/emm.2014.88

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cellular immunotherapy with ex vivo expanded cord blood T cells in a humanized mouse model of EBV-associated lymphoproliferative disease2015

    • Author(s)
      Matsuda G, Imadome K-I, Kawano F, Mochizuki M, Ochiai N, Morio T, Shimizu N, and Fujiwara S
    • Journal Title

      Immunotherapy

      Volume: 7 Issue: 4 Pages: 335-341

    • DOI

      10.2217/imt.15.2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reproduction of Epstein-Barr virus infection and pathogenesis in humanized mice2014

    • Author(s)
      Fujiwara S.
    • Journal Title

      Immune Network

      Volume: 14 Issue: 1 Pages: 1-6

    • DOI

      10.4110/in.2014.14.1.1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Preclinical studies of novel therapies for Epstein-Barr virus-associated diseases in humanized mouse models2014

    • Author(s)
      Imadome K, Matsuda G, Kawano F, Kodama E, Arai A, Shimizu N, Fujiwara S
    • Organizer
      39th Annual International Herpesvirus Workshop
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2014-07-20 – 2014-07-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Applications of mouse models of EBV-associated diseases for the evaluation of novel therapies2014

    • Author(s)
      Imadome K, Matsuda G, Kawano F, Kodama E, Arai A, Shimizu N, Fujiwara S
    • Organizer
      16th International Symposium on EBV and Associated Diseases
    • Place of Presentation
      Brisbane, Australia
    • Year and Date
      2014-07-16 – 2014-07-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] EBウイルス関連疾患の病態を再現するモデルマウス2014

    • Author(s)
      藤原成悦
    • Organizer
      第11回EBウイルス研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-06-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Reproduction and Analysis of Epstein-Barr Virus Pathogenesis in Humanized Mice2013

    • Author(s)
      Fujiwara S.
    • Organizer
      4th International Workshop on Humanized mice
    • Place of Presentation
      Seoul
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Reproduction of Epstein-Barr Virus-Associated Lymphoproliferative Diseases in Humanized Mice2013

    • Author(s)
      Fujiwara S.
    • Organizer
      Fall Conference of the Korean Association of Immunologists
    • Place of Presentation
      Seoul
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] Humanized Mice for HIV Research2015

    • Author(s)
      Fujiwara S, Matsuda G, and Imadome K
    • Total Pages
      16
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Remarks] 国立成育医療研究センター研究所母児感染研究部の研究内容

    • URL

      http://server45.joeswebhosting.net/~nr04581/infection/res.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 国立成育医療研究センター研究所母児感染研究部の研究内容

    • URL

      http://server45.joeswebhosting.net/~nr04581/infection/res.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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