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

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390414
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Osaka 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
• Keywords: 腎移植 / 免疫寛容

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [Presentation] A superagonistic monoclonal antibody for CD28 induced donor-specific tolerance (2007)
  • 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
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/jp/kastudo/kifu.html