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Role of the Cytokine Profiles Produced by iNKT Cells in the Initial Phase of Cyclophosphamide-Induced Tolerance^1

Research Project

Project/Area Number 18390380
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKyushu University

Principal Investigator

TOMITA Yukihiro  Kyushu University, Department of Cardiovascular Surgery, Faculty of Medicine, Associate Professor (90180174)

Co-Investigator(Kenkyū-buntansha) YOSHIKAI Yasunobu  Kyushu University, Research Center for Prevention of Infectious Diseases, Medical Institute of Bioregulation, Professor (90158402)
TANOUE Yoshihisa  KYUSHU UNIVERSITY, Department of Cardiovascular Surgery Faculty of Medicine, Assistant Professor (40372742)
梶原 隆  九州大学, 大学病院, 医員 (30403942)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥17,510,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2006: ¥8,800,000 (Direct Cost: ¥8,800,000)
Keywordstolerance / cyclophosphamide / NKT cell / NKT KO mouse / chimerism / cyclophosphamide / cyclophosphamlde / NKT KOマウス
Research Abstract

Cyclophosphamide (CP) -induced tolerance is a mixed chimerism-based tolerance induction protocol. Recently, we reported that invariant natural killer T (iNKT) cells were essential for the tolerance induction in this system. In this study we evaluated the roles of the cytokines produced by iNKT cells. DBA/2 (H-2^d) mice and BALB/c(H-2^d)wild-type (WT) or iNKT knockout (KO) mice were used as donors and recipients. WT recipients received three doses(days -7. -4, -1 or 35, 38, 41)or a single dose (day -1 or 0) of a-galactosylceramide (GC) in conjunction with our conditioning regimen, which consisted of 10^8 donor spleen cells (SC) on day 0 and 200 mg/kg CP on day 2. To investigate the iNKT cell function, iNKT KO recipients were reconstituted with cytokine(IFN-y. IL-4,or IL-10)KO iNKT cells and received donor SC and CP.
Mixed chimerism was observed in WT recipients, but was reduced in iNKT KO recipients. However, mixed chimerism was absent in WT recipients given GC on days -7, -4, -1, but not in WT recipients given GC on day 35, 38, 41. Donor skin grafts were chronically rejected when mixed chimerism was diminished. Skin grafts were accepted in iNKT KO recipients reconstituted with iNKT cells from IFN-y, IL-4, or IL-10 KO mice and receiving our conditioning regimen. iNKT cells were required in the initial phase of the induction of chimerism. Our results indicated that known major cytokines produced by iNKT cells were dispensable for the regulatory function of iNKT cells.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (15 results)

All 2008 2007 2006 Other

All Journal Article (10 results) (of which Peer Reviewed: 6 results) Presentation (5 results)

  • [Journal Article] Application of Cyclophsphamide-induced Tolerance in al,3-galactosyltransferase Knockout Mice Presensitized with Galal-3Galβ-4-GlcNAc Antigens.2008

    • Author(s)
      Tatsushi, Onzuka, Ichiro, Shimizu, Yukihiro, Tomita, Toshiro, Iwai, Shinji, Okano, Ryuji, Tominaga
    • Journal Title

      Surgery Today (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Immunoregulatory role of Natural Killer T Cells in Cyclophosphamide-Induced Tolerance2007

    • Author(s)
      Toshiro lwai
    • Journal Title

      Transplantation 84

      Pages: 1686-1695

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of Cyclosporin A in the Activation of Natural Killer T Cells Induced by aGalactosylceramide2007

    • Author(s)
      Takashi kajiwara
    • Journal Title

      Transplantation 83

      Pages: 184-192

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Influence of the Th1/Th2 paradigm for the regulatory function of the natural killer T (NKT) cells in cyclophosphamide (CP)-induced tolerance2007

    • Author(s)
      Tatsushi Onzuka
    • Journal Title

      American Journal of Transplantation (Supp.) 7

      Pages: 485-485

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The Immunoregulatory Roles of Natural Killer T Cells in Cyclophosphamide-Induced Tolerance.2007

    • Author(s)
      Iwai, T., Y., Tomita, I., Shimizu, T., Kajiwara, T., Onzuka, S., Okano, Y., Yasunami, Y., Yoshikai, K., Nomoto, R., Tominaga
    • Journal Title

      Transplantation 84

      Pages: 1686-1695

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Influence of the Th1/Th2 paradigm for the regulatory function of the natural killer T (NKT) cells in cyclophosphamide (CP)-induced tolerance.2007

    • Author(s)
      Tatsushi, Onzuka, Ichiro, Shimizu, Yukihiro, Tomita, Toshiro, Iwai, Shinji, Okano, Ryuji, Tominaga
    • Journal Title

      American Journal of Transplantation(Supp.) 7

      Pages: 485-485

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Immunoregulatory role of Natural Killer T Cells in Cydophosphamide-lnduced Tolerance2007

    • Author(s)
      Toshiro Iwai
    • Journal Title

      Transplantation 84

      Pages: 1686-1695

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Cyclosporirn A in the Activation of Natural Killer T Cells Induced by a-Galactosylceramide2007

    • Author(s)
      Takashi kajiwara
    • Journal Title

      Transplantation 83

      Pages: 189-192

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance2006

    • Author(s)
      Toshiro Iwai, Yukihiro Tomita, et al.
    • Journal Title

      The Journal of Immunology 177(12)

      Pages: 8400-9

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Application of Cyclophsphamide-induced Tolerance in al,3-galactosyltransferase Knockout Mice Presensitized with Gala l-3Galβ-4-G1cNAc Antigens

    • Author(s)
      Tatsushi Onzuka
    • Journal Title

      Surgery Today (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Presentation] Cyclophosphamide (CP) 誘導性免疫寛容におけるNKT細胞の調節性機序2007

    • Author(s)
      恩塚 龍士
    • Organizer
      日本移植学会
    • Place of Presentation
      仙台
    • Year and Date
      2007-11-23
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cyclophosphamide (CP)誘導性免疫寛容におけるNKT細胞の調節性機序2007

    • Author(s)
      恩塚 龍士
    • Organizer
      日本移植学会
    • Place of Presentation
      仙台
    • Year and Date
      2007-11-23
    • Related Report
      2007 Annual Research Report
  • [Presentation] Influence of the Th1/Th2 paradigm for the regulatory function of the natural killer T (NKT) cells in cyclophosphamide (CP)-induced tolerance2007

    • Author(s)
      Tatsushi Onzuka
    • Organizer
      American Transplant Congress
    • Place of Presentation
      San Francisco
    • Year and Date
      2007-05-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Influence of the Th1/Th2 paradigm for the regulatory function of the natural killer T(NKT) cells in cyclophosphamide(CP) -induced tolerance.2007

    • Author(s)
      Tatsushi, Onzuka, Ichiro, Shimizu, Yukihiro, Tomita, Toshiro, Iwai, Shinji, Okano, Ryuji, Tominaga
    • Organizer
      American Transplant Congress
    • Place of Presentation
      San Francisco
    • Year and Date
      2007-05-07
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Influence of the Th1/Th2 paracligm for the regulatory function of the natural killer T(NKT)cells in cyclolphosphamide (CP)-induced tolerance2007

    • Author(s)
      Tatushi Onzuka
    • Organizer
      American TransPlant Congress
    • Place of Presentation
      San Francisco
    • Year and Date
      2007-05-07
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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