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cyclophosphamide plus Busulfan-induced tolerance in rat into mouse xenotransplantation

Research Project

Project/Area Number 13671242
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TOMITA Yukihiro  Department of cardiovascular surgery Faculty of Medicine, Assistant Professor, 大学院・医学研究院, 講師 (90180174)

Co-Investigator(Kenkyū-buntansha) NISHIDA Takahiro  Department of cardiovascular surgery FacultyofMedicine, Assistant Professor, 医学部付属病院, 助手 (50284500)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥3,100,000 (Direct Cost: ¥3,100,000)
Keywordscyclophosphamide / Busulfan / tolerance / anti-alpha Gal nAb / alpha-Gal knockout mouse / xenotransplantation / hyperacute rejection / B cell tolerance / B細胞
Research Abstract

We have recently reported a new method of cyclophosphamide(CP) plus Busulfan (BU)-induced tolerance. Recently, we could established a modified method to induce both permanent mixed chimerism and skin allograft tolerance in H-2 mismatched combinations (J Immunol 2000; 164: 34). Our present protocol consists on injection of 1 x 10^8 allogeneic spleen cells (SC) on day 0, and administration of 200mg/kg CP and 30mg/kg BU on day 2 followed by 1 x 10^7 T cell-depleted donor bone marrow cells (BMC) on day 3. As a consequence, we also found that the correlation between the establishment of mixed chimerism and skin allograft tolerance and the clonal destruction as the major mechanisms of tolerance induction. In the present study, we applied our new system to rat into mouse xenograft tolerance. Mixed chimerism was detectable (5-20%) at 2-8 weeks after treatments, and F344 rat skins were significantly and specifically prolonged (median 40 days, max 75 days). However, neither permanent mixed chimerism nor skin xenograft tolerance could not be induced. NK cell-depletion did not permit more profound degree of mixed chimerism or induce more skin graft prolongation.. The present study indicated that our new protocol can induce temporal mixed chimerism and moderate skin graft polongation in a donor specific manner.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Tomita, Y., Q-W.Zhang, I.Shimizu, T.Iwai, S.Okano, K.Nomoto et al.: "Fractionated dosing of cyclophosphamide prevents leucopenic side effects in cyclophosphamide-induced tolerance"Surg.Today. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwai, T., Y.Tomita, Y.Yasunami, I.Shimizu, H.Yasui.: "The essential roles of NKT cells in cyclophosphamide-induced tolerance"Transplantation (Supp.). 74(4). 322-322 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu, I., Y.Tomita, H.Yasui.: "Induction of B cell tolerance against Gal-alpha(1-3) Gal Ag in cyclophosphamide (CP)-induced tolerance"Transplantation (Supp.). 74(4). 316-316 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, Y., I.Shimizu, T.Iwai, H.Yasui.: "The downmodulation of the Ly-49A induces efficient activation of NK cells"Transplantation (Supp.). 74(4). 254-254 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwai, T, Y.Tomita, Q-W Zhang, S.Okano, I.Shimizu, R.Minagawa et al.: "The Requirement of higher degree of chimerism for the induction of skin allograft tolerance in cyclophosphamide-induced tolerance"Transplant.Int.. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu, L, Y.Tomita, T.Iwai, G.Matsuzaki, K.Nomoto, H.Yasui.: "Different expressions of Ly-49 receptors on mouse NK and NK cells"Immunobiol.. 204. 466-476 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, Y., Q-W. Zhang, I. Shimizu, T. Iwai, S. Okano, K. Nomoto et al: "Fractionated dosing of cyclophosphamide prevents leucopenic side effects in cyclophosphamide-induced tolerance."Surg. Today. In press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwai, T. Tomita, Y. Yasunami, I. Shimizu, and H. Yasui.: "The essential roles of NKT cells in cyclophosphamide-induced tolerance."Transplantation(Supp.). 74. 322 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu, I., Y. Tomita, and H. Yasui.: "Induction of B cell tolerance against Gal-alpha(1-3) Gal Ag in cyclophosphamide (CP)-induced tolerance."Transplantation(Supp.). 74. 316 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, Y., I. Shimizu, T. Iwai and H. Yasui.: "The downmodulation of the Ly-49A induces efficient activation of NK cells"Transplantation(Supp.). 74. 316 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwai, T. Y.Tomita Q-W Zhang, S. Okano, I. Shimizu R. Minagawa et. Al: "The Requirement of higher degree of chimerism for the induction of skin allograft tolerance in cyclophosphamide-induced tolerance."Transplant. Int.. In Press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu, I., Y. Tomita, T. Iwai, G. Matsuzaki, K. Nomoto, and H. Yasui.: "Different expressions of Ly-49 receptors on mouse NK and NK cells."Immunobiol.. 204. 466-476 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, Y., Q-W.Zhang, I.Shimizu, T.Iwai, S.Okano, K.Nomoto et al.: "Fractionated dosing of cyclophosphamide prevents leucopenic side effects in cyclophosphamide-induced tolerance"Surg. Today. (In Press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwai, T., Y.Tomita, Y.Yasunami, I.Shimizu, H.Yasui: "The essential roles of NKT cells in cyclophosphamide-induced tolerance"Transplantation (Supp.). 74(4). 322 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimizu, I., Y.Tomita, H.Yasui: "Induction of B cell tolerance against Gal-alpha(1-3) Gal Ag in cyclophosphamide (CP)-induced tolerance"Transplantation (Supp.). 74(4). 316 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tomita, Y., I.Shimizu, T.Iwai, H.Yasui: "The downmodulation of the Ly-49A induces efficient activation of NK cells"Transplantation (Supp.). 74(4). 254 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwai, T, Y.Tomita, Q-W.Zhang, S.Okano, I.Shimizu, R.Minagawa et al.: "The Requirement of higher degree of chimerism for the induction of skin allograft tolerance in cyclophosphamide-induced tolerance"Transplant. Int.. (In Press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimizu, I., Y.Tomita, T.Iwai, G.Matsuzaki, K.Nomoto, H.Yasui: "Different expressions of Ly-49 receptors on mouse NK and NK cells"Immunobiol. 204. 466-476 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tomita, Y., Q-W.Zhang, I.Shimizu, T.Iwai et al.: "Fractionated dosing of cyclophosphamide prevents leucopenic side effects in cyclophosphamide-induced tolerance"Surgery Today. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimizu, I., Y.Tomita, T.Iwai, G.Matsuzaki, K.Nomoto et al.: "Different expressions of Ly-49 receptors on mouse NK and NK cells"Immunobiology. 204. 466-476 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Zhang, Q-W., Y.Tomita, G.Matsuzaki, S.Okano, I.Shimizu: "Induction of heart allograft tolerance without development of post-transplant cardiac allograft vasculopathy in chimerism-based drug-induced tolerance"Transplantation. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Zhang, Q-W., Y.Tomita, G.Matsuzaki, T.Uchida, et al.: "Chronic rejection of H-2 matched heart allografts : Early emergence of vasculopathy, alloantibody and accumulation of IFN-g and IL-10 mRNA"Transplantation. 14. 143-152 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomita, Y., Q-W.Zhang, T.Uchida, M.Yoshikawa, U.Shimizu: "A technique of cervical aortic graft transplantation in mice"J Heart Lung Transplantation. 20. 699-702 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomita, Y., Yoshikawa, M., Q-W.Zhang, I.Shimizu, S.Okano et al.: "Induction of mixed chimerism and permanent skin graft tolerance by additional myelosuppressive treatments across fully H-2 mismatched barriers in mice primed with・・・"J. Immunology. 165. 34-41 (2000)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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