GVHD・GVLに関わる新たなドナーT細胞活性化のメカニズム

2009 Fiscal Year Annual Research Report

• Project/Area Number: 21390295
• Research Institution: Kyushu University
• Principal Investigator: 豊嶋 崇徳 Kyushu University, 大学病院, 准教授 (40284096)
• Keywords: GVHD / GVL / T細胞 / 樹状細胞 / 形質細胞様樹状細胞 / Toll like receptor

Research Abstract

MyD88-/-マウスとTRIF-/-マウスを交配し,TRIF/MyD88-/-マウスを作成した.MyD88-/-マウスあるいはTRIF-/-マウスをドナーとした骨髄移植ではGVHDの重症度に変化はみられなかった。一方、TRIF/MyD88-/-ドナーからの移植ではGVHDの劇的な軽症化が観察された.次に,骨髄細胞は野生型ドナーより、T細胞はTRIF/MyD88-/-ドナーより移植したところやはりGVHDの軽症化がみられ、T細胞上に発現するToll like receptor(TLR)を介するシグナルがドナーT細胞活性化に重要であることが確認された。また、われわれの開発した各抗原提示細胞のGVHD惹起能をin vivoで検討できる系を用い、形質細胞様樹状細胞(pDC)のGVHD誘導能を検討した。その結果通常のconventional DC(cDC)非存在下で,pDC単独でドナーT細胞活性化がおこり、GVHDが発症することが示された。このGVHDは臨床的、病理学的に、cDCによって誘導されるGVHDと全く同様であった。pDCによるGVHD誘導効果の発現には、移植前処置によるpDCの活性化が必須で、MHCクラスII分子依存性であったが、TLRシグナル非依存性であった。

Research Products

• [Journal Article] Improved outcome of allogeneic bone marrow transplantation due to breast-feeding-induced tolerance to maternal antigens (2009)
  • Author(s): Aoyama K, Koyama M, Matsuoka KI, Hashimoto D, Ichinohe T, Harada M, Akashi K, Tanimoto M, Teshima T
  • Journal Title: Blood 113 Pages: 1829-1833
  • Peer Reviewed
• [Journal Article] Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells (2009)
  • Author(s): Koyama M, Hashimoto D, Aoyama K, Matsuoka KI, Karube K, Niiro H, Harada M, Tanimoto M, Akashi K, Teshima T
  • Journal Title: Blood 113 Pages: 2088-2095
  • Peer Reviewed
• [Journal Article] Oral valganciclovir as preemptive therapy is effective for cytomega lovirus infection in allogeneic hematopoietic stem cell transplantation (2009)
  • Author(s): Takenaka K, Eto T, Nagafuji K, Kamezaki K, Matsuo Y, Yoshimoto G, Harada N, Yoshida M, Henzan H, Takase K, Miyamoto T, Akashi K, Harada M, Teshima T
  • Journal Title: Int J Hematol 89 Pages: 318-323
  • Peer Reviewed
• [Journal Article] Rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease (2009)
  • Author(s): Teshima T, Nagafuji K, Henzan H, Miyamura K, Takase K, Hidaka M, Miyamoto T, Takenaka K, Akashi K, Harada M
  • Journal Title: Int J Hematol 90 Pages: 253-260
  • Peer Reviewed
• [Journal Article] Infectious complications in patients receiving autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune disease (2009)
  • Author(s): Kohno K, Nagafuji K, Tsukamoto H, Horiuchi T, Takase K, Aoki K, Henzan H, Kamezaki K, Takenaka K, Miyamoto T, Teshima T, Harada M, Akashi K
  • Journal Title: Transpl Infect Dis 11 Pages: 318-323
  • Peer Reviewed
• [Journal Article] Nonmyeloablative allogeneic hematopoietic stem cell transplantation as immunotherapy for pancreatic cancer (2009)
  • Author(s): Abe Y, Ito T, Baba E, Nagafuji K, Kawabe K, Choi I, Arita Y, Miyamoto T, Teshima T, Nakano S, Harada M
  • Journal Title: Pancreas 38 Pages: 815-819
  • Peer Reviewed
• [Journal Article] Second unrelated cord blood transplantation using a reduced conditioning regimen combined with gemtuzumab ozogamicin in patients with relapsed acute myelogenous leukemia (2009)
  • Author(s): Yamauchi T, Mori Y, Miyamoto T, Kamezaki K, Aoki T, Yamamoto A, Takenaka K, Iwasaki H, Harada N, Nagafuji K, Teshima T, Akashi K
  • Journal Title: Int J Hematol 90 Pages: 416-420
  • Peer Reviewed
• [Presentation] マウスGVHDモデルにおける移植後長期の制御性T細胞再構築の検討 (2011)
  • Author(s): 杉山暖子、前田嘉信、西森久和、小林孝一郎、山筋好子、竹内賢吾, 豊嶋崇徳、谷本光音
  • Organizer: 第32回日本造血細胞移植学会総会
  • Place of Presentation: 浜松
  • Year and Date: 20110219-20110220
• [Presentation] R-spondinlは移植前処置から腸管を保護し、移植片対宿主病(GVHD)を改善する. (2010)
  • Author(s): 高嶋秀一郎, 門脇賢典、青山一利, 小山幹子, 大島毅、富塚一磨、赤司浩一, 原田実根, 豊嶋崇徳
  • Organizer: 第32回日本造血細胞移植学会総会
  • Place of Presentation: 浜松
  • Year and Date: 20100219-20100220
• [Presentation] 同種造血幹細胞移植後のHematogonesは良好な移植経過を反映する (2010)
  • Author(s): 島隆弘、宮本敏浩, 菊繁吉謙、亀崎健次郎、竹中克斗、豊嶋崇徳, 赤司浩一
  • Organizer: 第32回日本造血細胞移植学会総会
  • Place of Presentation: 浜松
  • Year and Date: 20100219-20100220
• [Presentation] Cyclosporine, but not mTOR inhibitors, hampers the reconstitution of bone marrow-derived Tregs (2009)
  • Author(s): Sugiyama H, Maeda Y, Nishimori H, Kobayashi K, Takeuchi K, Teshima T, Tanimoto M
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 20091023-20091025
• [Presentation] Depletion of regulatory T cells causes chronic GVHD in experimental bone marrow transplantation (2009)
  • Author(s): Kadowaki M, Sakoda Y, Takashima S, Aoyama K, Koyama M, Hashimoto D, Akashi K, Teshima T
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 20091023-20091025
• [Presentation] Successful treatment of 8p11 myeloproliferative syndrome with allogeneic stem cell transplantation (2009)
  • Author(s): Yamauchi T, Kouno K, Yamamoto A, Shima T, Yoshida S, Mori Y, Kamezaki K, Takenaka K, Harada N, Nagafuji K, Miyamoto T, Teshima T, Iwasaki H, Akashi K
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 20091023-20091025
• [Presentation] Rituximab improves the outcome of newly diagnosed diffuse-large B-cell lymphoma following auto-PBSCT (2009)
  • Author(s): Kamezaki K, Takenaka K, Mori Y, Numata A, Harada N, Miyamoto T, Nagafuji K, Teshima T, Harada M, Akashi K
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 20091023-20091025
• [Presentation] Additional acquisition of t(1 ; 21)in a patient relapsing with AML with NUP98-HOXA9 (2009)
  • Author(s): Aoki T, Miyamoto T, Yoshida S, Yamamoto A, Kamezaki K, Iwasaki H, Takenaka K, Harada N, Teshima T, Akashi K
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 20091023-20091025
• [Presentation] Reduced intensity cord blood transplantation with GO for relapsed AML patients (2009)
  • Author(s): Mori Y, Yamauchi T, Miyamoto T, Aoki T, Yamamoto A, Kamezaki K, Takenaka K, Iwasaki H, Harada N, Nagafuji K, Teshima T, Akashi K
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 20091023-20091025
• [Presentation] Activation of PD-1/PD-L1 interaction by graft-versus-host disease para doxically impairs GVL effects (2009)
  • Author(s): Takashima S, Asakura S, Hashimoto D, Tanimoto M, Akashi K, Teshima T
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 20091023-20091025
• [Book] ガイドラインパースペクティブ造血幹細胞移植 (2009)
  • Author(s): 豊嶋崇徳編
  • Total Pages: 71-83
  • Publisher: 医薬ジャーナル社