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

• 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
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥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.

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] 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
  • Peer Reviewed
• [Journal Article] The CECL12 (SDF-1)/CXCR4 Axis is Essential for the Development of Renal Vasculature (2009)
  • Author(s): Takabatake Y, Sugiyama T, Kohara H, Matsusake T, et al
  • Journal Title: J Am Soc Nephrol 20 Pages: 1714-23
  • 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
• [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
  • NAID: 40016324087
• [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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Participation of autophagy in renal ischemial/reperfusion injury (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Chemically modified siRNA prolonged RNA interference in renal disease (2007)
  • 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
  • Peer Reviewed
• [Journal Article] HGF-MSP chimera protects kidneys from ischemia-reperfusion injury (2007)
  • 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
  • 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
• [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
• [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
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/jp/kastudo/kifu.html