Induction of tolerance by B cell regulation in the organ ransplantation

• Project/Area Number: 21591650
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Keio University
• Principal Investigator: FUCHIMOTO Yasushid 慶應義塾大学, 医学部, 共同研究員 (40219077)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 移植 / B細胞 / ドナー特異的免疫寛容 / Rituximab / 血液型不適合 / MHC / 血液不適合肝移植 / リツキサン / B細胞免疫 / humanized-NOGマウス / αGal-knock outマウス / 血液型不適合肝移植 / B細胞免疫寛容

Research Abstract

It was known that B cells played an important role as well as T cells for acute and chronic rejection. We sensitized B cells in the patients of blood type incompatibility liver transplantation and the bone marrow transplantation, with a donor antigen using humanized-NOG mouse in ex-vivo and evaluated donor antibody production ability. As a result, it was shown that reactive B-cell clones were removed at the stage when immature B cells matured by the antigens in the organ and induced the tolerance. The suppression of the chronic rejection, the possibility that, besides, tolerance was obtained for T-cell immunity were demonstrated by B-cell removal.

Research Products

• [Journal Article] (2012)
  • Author(s): Shinoda M, Tanabe M, Kawachi S, Ono Y, Hayakawa T, Iketani O, Kojima M, Itano O, Obara H, Kitago M, Hibi T, Matsubara K, Shimojima N, Fuchimoto Y, Hoshino K, Wakabayashi G, Shimazu M, Tanigawara Y, Kuroda T, Morikawa Y, Kitajima M, Kitagawa Y
  • Journal Title: Transplant Proc Volume: 44(5) Pages: 1329-35
  • Peer Reviewed
• [Journal Article] Vincristine, actinomycinD, cyclophosphami de chemotherapy resolves Kasabach-Merritt Syndrome resistant to conventional therapies (2012)
  • Author(s): Fuchimoto Y, Morikawa N, Kuroda T, Hirobe S, Kamagata S, Kumagai M, Matsuoka K, Morikawa Y
  • Journal Title: Pediatr Int Volume: 54(2) Pages: 285-7
  • Peer Reviewed
• [Journal Article] Vincristine, actinomycin D, cyclophosphamide chemotherapy resolves Kasabach-Merritt syndrome resistant to conventional therapies. (2012)
  • Author(s): Fuchimoto Y, Morikawa N, Kuroda T, Hirobe S, Kamagata S, Kumagai M, Matsuoka K, Morikawa Y.
  • Journal Title: Pediatr Int. Volume: 54 Issue: 2 Pages: 285-287
  • DOI: 10.1111/j.1442-200x.2011.03414.x
  • Peer Reviewed
• [Journal Article] Cyclosporine A-based immunotherapy in adult living donor liver transplantation : accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion (2011)
  • Author(s): Hibi T, Tanabe M, Hoshino K, Fuchimoto Y, Kawachi S, Itano O, Obara H, Shinoda M, Shimojima N, Matsubara K, Morikawa Y, Kitagawa Y
  • Journal Title: Transplantation Volume: 92(1) Pages: 100-5
  • Peer Reviewed
• [Journal Article] A long-term survival case of tracheal agenesis : management for tracheoesophageal fistula and esophageal reconstruction (2011)
  • Author(s): Fuchimoto Y, Mori M, Takasato F, Tomita H, Yamamoto Y, Shimojima N, Hoshino K, Koinuma G, Morikawa Y
  • Journal Title: Pediatr Surg Int Volume: 27(1) Pages: 103-6
  • Peer Reviewed
• [Journal Article] Survival of a congenital ileal atresia infant weighing 359 g at birth after laparotomy (2011)
  • Author(s): Fuchimoto Y, Tomita H, Takasato F, Yamamoto Y, Mori M, Shimojima N, Hoshino K, Hokuto I, Ikeda K, Morikawa Y
  • Journal Title: Pediatr Int Volume: 53(1) Pages: 127-8
  • NAID: 10029557456
  • Peer Reviewed
• [Journal Article] 総排泄腔奇形根治術後遠隔期に発症し、診断に苦慮した慢性腹痛・腹壁痛: ACNES(abdominal cutaneous nerve entrapment syndrome)の1例 (2011)
  • Author(s): 富田紘史, 下島直樹, 有末篤弘, 高里文香, 森昌玄, 山本裕輝, 渕本康史, 星野健, 津崎晃一, 森川康英
  • Journal Title: 日本小児外科学会雑誌 Volume: 47(6) Pages: 948-952
  • NAID: 110008790677
  • Peer Reviewed
• [Journal Article] 【小児における消化管機能障害の診断と治療】小児慢性便秘におけるevoked-HAPC測定の有用性 (2011)
  • Author(s): 富田紘史, 星野健, 有末篤弘, 高里文香, 森昌玄, 山本裕輝, 下島直樹, 渕本康史, 田波穣, 森川康英
  • Journal Title: 小児外科 Volume: 43(6) Pages: 606-611
• [Journal Article] 直腸肛門奇形研究科JASGAP委員会:患者のQOLに与える影響を考慮した新たな排便機能評価試案の検討(第1報) (2011)
  • Author(s): 上野滋, 森川康英, 岩井潤, 奥山直樹, 越永従道, 鈴木則夫, 高松英夫, 田口智章, 渕本康史, 松藤凡, 八木誠
  • Journal Title: 日本小児外科学会雑誌 Volume: 47(1) Pages: 35-46
• [Journal Article] A long-term survival case of tracheal agenesis : management for tracheoesophageal fistula and esophageal reconstruction (2011)
  • Author(s): 渕本康史
  • Journal Title: Pediatr Surg Int Volume: 27 Issue: 1 Pages: 103-6
  • DOI: 10.1007/s00383-010-2716-0
  • Peer Reviewed
• [Journal Article] Survival of a congenital ileal atresia infant weighing 359 g at birth after laparotomy (2011)
  • Author(s): 渕本康史
  • Journal Title: Pediatr Int Volume: 53 Issue: 1 Pages: 127-8
  • DOI: 10.1111/j.1442-200x.2010.03283.x
  • NAID: 10029557456
  • Peer Reviewed
• [Journal Article] Cyclosporine A-based immunotherapy in adult living donor liver transplantation : accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion (2011)
  • Author(s): 日比泰造、渕本康史
  • Journal Title: Transplantation Volume: 92 Issue: 1 Pages: 100-5
  • DOI: 10.1097/tp.0b013e31821dcae3
  • Peer Reviewed
• [Journal Article] 患者のQOLに与える影響を考慮した新たな排便機能評価試案の検討(第1報) (2011)
  • Author(s): 上野滋、渕本康史
  • Journal Title: 日本小児外科学会雑誌 Volume: 47 Pages: 35-46
  • NAID: 110008506455
  • Peer Reviewed
• [Journal Article] 【小児における消化管機能障害の診断と治療】小児慢性便秘におけるevoked-HAPC測定の有用性 (2011)
  • Author(s): 富田紘史、渕本康史
  • Journal Title: 小児外科 Volume: 43 Pages: 606-11
• [Journal Article] 総排泄腔奇形根治術後遠隔期に発症し、診断に苦慮した慢性腹痛・腹壁痛:ACNES (abdominal cutaneous nerve entrapment syndrome)の1例 (2011)
  • Author(s): 富田紘史、渕本康史
  • Journal Title: 日本小児外科雑誌 Volume: 43 Pages: 948-52
  • NAID: 110008790677
  • Peer Reviewed
• [Journal Article] A long-term survival case of tracheal agenesis : management for tracheoesophageal fistula and esophageal reconstruction. (2011)
  • Author(s): Fuchimoto Y, Hoshino K, Morikawa Y., et al
  • Journal Title: Pediatr Surg Int. Volume: 27 Pages: 103-106
  • Peer Reviewed
• [Journal Article] Idiopathic hypereosinophilic syndrome in a case with ABO-incompatible liver transplantation for biliary atresia complicated by portal vein thrombosis (2010)
  • Author(s): Yamada Y, Hoshino K, Shimojima N, Shinoda M, Obara H, Kawachi S, Fuchimoto Y, Tanabe M, Kitagawa Y, Morikawa Y
  • Journal Title: Pediatr Transplant Volume: 14(5)
  • Peer Reviewed
• [Journal Article] 【高位鎖肛基礎から臨床の最前線まで】新たな排便機能評価試案について (2010)
  • Author(s): 上野滋, 森川康英, 岩井潤, 奥山直樹, 越永従道, 鈴木則夫, 高松英夫, 田口智章, 渕本康史, 松藤凡, 八木誠
  • Journal Title: 小児外科 Volume: 42(11) Pages: 1145-1150
• [Journal Article] 高アンモニア血症と門脈異常 (2010)
  • Author(s): 山本裕輝, 星野健, 高里文香, 富田紘史, 森昌玄, 下島直樹, 渕本康史, 中原理紀, 茂松直之, 栗林幸夫, 森川康英
  • Journal Title: 小児科 Volume: 51(3) Pages: 341-347
  • Peer Reviewed
• [Journal Article] Idiopathic hypereosinophilic syndrome in a case with ABO-incompatible liver transplantation for biliary atresia complicated by portal vein thrombosis. (2010)
  • Author(s): Yamada Y, Hoshino K, Fuchimoto Y, Morikawa Y., et al
  • Journal Title: Pediatr Transplant Volume: 14
• [Presentation] Recurrence of Primary Sclerosing Cholangitis after Living Donor Liver Transplantation and Roles of B-Cell Depletion (2012)
  • Author(s): Fuchimoto Y, Tanabe M, Hoshino K, Yamada Y, Kawachi S, Itano O, Obara H, Kitagou M, Shinoda M, Shimojima N, Matsubara K, Kitagawa Y, Ohdan O, Kuroda T
  • Organizer: American Transplant Congress
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2012-06-04
• [Presentation] 小児臓器移植の未来-ドナー特異的免疫寛容の誘導- (2012)
  • Author(s): 渕本康史
  • Organizer: 第49回日本小児外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-05-16
• [Presentation] ドナー特異的免疫寛容の誘導-operational toleranceからmixed chimerismまで- (2011)
  • Author(s): 渕本康史
  • Organizer: 第47回日本移植学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2011-11-06
• [Presentation] ドナー特異的免疫寛容の誘導-operational toleranceからmixed chimerismまで- (2011)
  • Author(s): 渕本康史
  • Organizer: 第47回日本移植学会総会
  • Place of Presentation: 日本、福島
  • Year and Date: 2011-10-05
• [Presentation] Mechanism of donor-specific B-cell tolerance after ABO-incompatible infant liver transplantation (2011)
  • Author(s): Fuchimoto Y, Yamada Y, Hoshino K, Tanabe M, Kawachi S, Kitagawa Y, Ohdan H, Morikawa Y
  • Organizer: International Surgical Week
  • Place of Presentation: Yokohama, JA
  • Year and Date: 2011-08-30
• [Presentation] Mechanism of donor-specific B-cell tolerance after ABO-incompatible infant livertransplantation (2011)
  • Author(s): 渕本康史
  • Organizer: International Surgical Week
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2011-08-30
• [Presentation] Characterization of CD133+ cancer stem like cells in rhabdomyosarcoma cell lines (2011)
  • Author(s): 渕本康史
  • Organizer: International Surgical Week
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2011-08-28
• [Presentation] 原発性胆管炎に対する生体部分肝移植後の再発とB細胞除去の役割 (2011)
  • Author(s): 渕本康史、田邊稔、星野健、山田洋平、松原健太郎、下島直樹、篠田昌宏、北郷実、尾原秀明、板野理、河地茂行、北川雄光、黒田達夫
  • Organizer: 第29回肝移植研究会
  • Place of Presentation: 仙台
  • Year and Date: 2011-07-22
• [Presentation] Successful living donor liver transplantation for extrahepatic biliary atresia (post Kasai produce) accompanied by complex congenital heart anomalies with severe shunt (2011)
  • Author(s): 星野健、渕本康史
  • Organizer: 6thCongress of the International Pediatric Transplant Association, Montreal
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2011-06-27
• [Presentation] Mechanism of donor-specific B-cell tolerance after ABO-incompatible infant liver transplantation (2011)
  • Author(s): Fuchimoto Y, Yamada Y, Tanabe M, Hoshino K, Matsubara K, Shimojima N, Shinoda M, Obara H, Itano O, Kawachi S, Kitagawa Y, Ohdan H, Morikawa Y
  • Organizer: 6^<th> Congress of the International Pediatric Transplant Association
  • Place of Presentation: Montreal, CA
  • Year and Date: 2011-06-26
• [Presentation] donor-specific B-cell tolerance after ABO-incompatible infant liver transplantation (2011)
  • Author(s): 渕本康史
  • Organizer: 6thCongress of the International Pediatric Transplant Association, Montreal
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2011-06-26
• [Presentation] Characterization of CD133+ cancer stem like cells in rhabdomyosarcoma cell lines : ORAL PRESENTATION (2011)
  • Author(s): 渕本康史
  • Organizer: 44^<th> Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: Cancun, Mexico
  • Year and Date: 2011-04-13
• [Presentation] Living-Related partial liver transplant for primary sclerosing cholangitis(PSC): post-transplant recurrence and preventative measures (2010)
  • Author(s): Fuchimoto Y, Hoshino K, Tanabe M, Yamada Y, Hibi T, Shimojima N, Shinoda M, Hideaki O, Kawachi S, Ohdan H, Kitagawa Y, Morikawa Y
  • Organizer: 23th International Congress of the Transplantation Society
  • Place of Presentation: Vancouver, CA
  • Year and Date: 2010-08-17
• [Presentation] 小児移植医療小児肝移植後リンパ増殖症(PTLD)に対するFACSを用いた迅速な診断とリツキシマブの治療適応の検討 (2010)
  • Author(s): 渕本康史, 星野健, 今留謙一, 大隅朋夫, 嶋田博之, 富田紘史, 高里文香, 山本裕輝, 森昌玄, 下島直樹, 日比泰三, 篠田昌弘, 尾原秀明, 河地茂行, 田辺稔, 北川雄光, 向井万起夫, 森川康英
  • Organizer: 第47回日本小児外科学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-06-19
• [Presentation] 骨髄-臓器composite graftによるドナー特異的免疫寛容誘導骨髄-臓器composite graftの作製 (2010)
  • Author(s): 渕本康史, 絵野澤伸, 梅澤明弘, 林奐, 森川康英
  • Organizer: 第47回日本小児外科学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-06-19
• [Presentation] 横紋筋肉腫細胞株におけるCD133の発現解析による抗癌剤耐性、腫瘍形成能の評価 (2010)
  • Author(s): 渕本康史
  • Organizer: 第47回日本小児外科学会学術集会
  • Place of Presentation: 愛知
  • Year and Date: 2010-06-19
• [Presentation] 原発性硬化性胆管炎(PSC)に対する生体肝移植後の再発とその対策法-HLA相同性ならびにB細胞除去の役割- (2010)
  • Author(s): 渕本康史, 星野健, 田邉稔, 山田洋平, 日比泰造, 下島直樹, 篠田昌宏, 尾原秀明, 河地茂行, 北川雄光, 森川康英
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-10