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Induction of kidney graft tplerance using donor-specofoc regulatory T cells

Research Project

Project/Area Number 19390414
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionOsaka University

Principal Investigator

TAKAHARA Shiro  Osaka University, 医学系研究科, 寄附講座教授 (70179547)

Co-Investigator(Kenkyū-buntansha) ISAKA Yoshitaka  大阪大学, 医学系研究科, 准教授 (00379166)
NASHII Ko  国立成育医療センター, 医科学研究所, 室長 (60321890)
AZUMA Haruhito  大阪医科大学, 医学系研究科, 准教授 (40231914)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2008: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Keywords腎移植 / 免疫寛容 / 腎臓移植 / 制御性T細胞 / superagonistCD28抗体 / Foxp3
Research Abstract

Regulatory T (Treg) cells play an important role in graft tolerance. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28SA), using rat acute renal allograft model (Wistar to Lewis). CD28SA induced marked infiltration of Treg cells into the allografts. 90% of recipients treated with CD28SA survived over 100 days, and 70% survived with well-preserved graft function until graft harvest at 180 days. Furthermore, these long-surviving recipients showed donor-specific tolerance. In conclusion, CD28SA treatment successfully induces donor-specific tolerance with the involvement of Treg cells, and thus the therapeutic value of this approach warrants further investigation and preclinical studies.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (17 results)

All 2009 2008 2007 Other

All Journal Article (13 results) (of which Peer Reviewed: 8 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Superagonist CD28 antibody preferentially expanded Foxp3-expressing nTreg cells and prevented graft-versus-host diseases.2009

    • Author(s)
      Kitazawa, Y. ; Fujino, M. ; Li, X.K. ; Xie, L. ; Ichimaru, N. ; Okumi, M. ; Nonomura, N. ; Tsujimura, A. ; Isaka, Y. ; Kimura, H. ; Hunig, T. ; Takahara, S.
    • Journal Title

      Cell transplantation 18(5)

      Pages: 627-637

    • Related Report
      2009 Final Research Report
  • [Journal Article] Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production.2009

    • Author(s)
      Xie, L. ; Li, X.K. ; Funeshima-Fuji, N. ; Kimura, H. ; Matsumoto, Y. ; Isaka, Y. ; Takahara, S
    • Journal Title

      Int Immunopharmacol 9(5)

      Pages: 575-581

    • Related Report
      2009 Final Research Report
  • [Journal Article] Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production.2009

    • Author(s)
      Xie L, Li XK, Funeshima-Fuji N, Kimura H, et al
    • Journal Title

      Int Immunopharmacol 9

      Pages: 575-581

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The CECL12 (SDF-1)/CXCR4 Axis is Essential for the Development of Renal Vasculature2009

    • Author(s)
      Takabatake Y, Sugiyama T, Kohara H, Matsusake T, et al
    • Journal Title

      J Am Soc Nephrol 20

      Pages: 1714-23

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Superagonistic CD28 antibody induces donor-specific tolerance in rat renal allografts.2008

    • Author(s)
      Azuma, H. ; Isaka, Y. Li, X. ; Hunig, T. ; Sakamoto, T. ; Nohmi, H. ; Takabatake, Y. ; Mizui, M. ; Kitazawa, Y. ; Ichimaru, N. ; Ibuki, N. ; Ubai, T. ; Inamoto, T. ; Katsuoka, Y. ; Takahara, S
    • Journal Title

      Am J Transplant 8(10)

      Pages: 2004-2014

    • Related Report
      2009 Final Research Report
  • [Journal Article] Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody can prevent rat cardiac allograft rejection.2008

    • Author(s)
      Kitazawa, Y. ; Fujino, M. ; Sakai, T. ; Azuma, H. ; Kimura, H. ; Isaka, Y. ; Takahara, S. ; Hunig, T. ; Abe, R. ; Li, X.K.
    • Journal Title

      J Heart Lung Transplant 27(4)

      Pages: 362-371

    • Related Report
      2009 Final Research Report
  • [Journal Article] CD28スーパーアゴニスト抗体による制御性T細胞の誘導2008

    • Author(s)
      猪阪善隆
    • Journal Title

      臨床免疫・アレルギー科 50(4号)

      Pages: 451-457

    • NAID

      40016324087

    • Related Report
      2009 Final Research Report
  • [Journal Article] Superagonistic CD28 antibody induces donor-specific tolerance in rat renalallografts.2008

    • Author(s)
      Azuma H, Isaka Y, Li X, Hunig T, et al.
    • Journal Title

      Am J Transplant 8

      Pages: 2004-14

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carbamylated erythropoietin improves angiogenesis and protects the kidneys from ischemia-reperfusion injury.2008

    • Author(s)
      Imamura R, Okumi M, Isaka Y, Ichimaru N, et al.
    • Journal Title

      Cell transplantation 17

      Pages: 135-141

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonerythropoietic derivative of erythropoietin protects against tubulointerstitialinjury in a unilateral ureteral obstruction model.2008

    • Author(s)
      Kitamura H, Isaka Y, Takabatake Y. Imamura R, et al.
    • Journal Title

      Nephrol Dial Transplant 23

      Pages: 1521-1528

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Participation of autophagy in renal ischemial/reperfusion injury2008

    • Author(s)
      Suzuki C, Isaka Y, Takabatake Y, Tanaka H, Koike M, Shibata M, Uchiyama Y, Takahara S, Imai E
    • Journal Title

      Biochemical and biophysical research communications 368

      Pages: 100-106

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemically modified siRNA prolonged RNA interference in renal disease2007

    • Author(s)
      Takabatake, Y., Y. Isaka, M. Mizui, H. Kawachi, S. Takahara, and E. Imai.
    • Journal Title

      Biochemical and biophysical research communications 363

      Pages: 432-437

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HGF-MSP chimera protects kidneys from ischemia-reperfusion injury2007

    • Author(s)
      Xue, F., Y. Isaka, T. Takahara, R. Imamura, C. Suzuki, N. Ichimaru, P. Michieli, and S. Takahara.
    • Journal Title

      Biochemical and biophysical research communications 363

      Pages: 451-456

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Systemic administration of siRNA targeting p53 protects kidneys from ischemia-reperfusion injury in experimental rat kidney transplantation model.2008

    • Author(s)
      Isaka Y
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      Philadelphia
    • Year and Date
      2008-11-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] A superagonistic monoclonal antibody for CD28 induced donor-specific tolerance2007

    • Author(s)
      Y Isaka, Y Takabatake, M Mizui, H Tanaka, X Li, H Azuma, T Hunig, R Imamura, N Ichimaru, E Imai, S Takahara
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Francisco USA
    • Year and Date
      2007-11-03
    • Related Report
      2009 Final Research Report
  • [Presentation] A Superagonistic Monoclonal Antibody for CD28 Induced Donor-Specific Tolerance.2007

    • Author(s)
      Isaka Y
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Francisco
    • Year and Date
      2007-11-03
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.osaka-u.ac.jp/jp/kastudo/kifu.html

    • Related Report
      2009 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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