GVHD/GVLに関わるメモリーT細胞分化のメカニズム

2014 Fiscal Year Research-status Report

• Project/Area Number: 25461453
• Research Institution: Kyushu University
• Principal Investigator: 加藤 光次 九州大学, 大学病院, 助教 (20571764)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: GVHD / メモリーT細胞

Outline of Annual Research Achievements

造血幹細胞移植の臨床検体を用い、現在各ドナーソース（HLA一致血縁、非血縁者間移植、臍帯血移植、ハプロ移植）での免疫再構築を、CD4およびCD8T細胞メモリー分画毎に、特に
ヒトメモリーT幹細胞分画(CD3+CD8+CD45RO-CCR7+CD45RA+CD62L+CD27+CD28+IL7Rα+CD95+)を中心に検討を行なっている。ヒトメモリーT幹細胞(Tmsc)が、マウスモデルで示されたような難治性GVHDの原因になっているかの検討について検討したが、その病的意義は少なく、予想に反して、免疫寛容に重要な役割が示唆された。他の移植ソースと異なり、特に，ハプロ移植の早期の免疫構築にTMSCが重要役割を果たしている可能性を示唆するデータをえており、同Tmsc細胞集団をソートし、遺伝子発現をマイクロアレイで検討、免疫寛容に関わる分子の同定をすすめている。また、他のドナーソースでは、長期の免疫再構築および慢性GVHDにTmscが重要であり、正常および病的なTmscの分子メカニズムの違いの検討もはじめている。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

造血幹細胞移植の臨床検体を用いた研究においては、ヒトではその役割が不明な部分が多いTmscの存在が確認され、正常免疫再構築における意義について、現象としてとらえることができた。今後は、そのメカニズムにせまる研究展開を行なっていく予定である。

Strategy for Future Research Activity

ハプロ移植後早期のTmsc細胞集団をソートし、遺伝子発現をマイクロアレイで検討、免疫寛容に関わる分子の同定をすすめていく。また長期の免疫再構築および慢性GVHDにTmscの分子メカニズムの違いについても、TCR　clonalityの解析をすすめ、急性期のものと比較する。

Research Products

• [Journal Article] Characteristics of patients with development of large granular lymphocytes expansion among dasatinib-treated patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic stem cell transplantation. (2015)
  • Author(s): Ito Y, Miyamoto T, Kamimura T, Aoki K, Henzan H, Aoki T, Shiratsuchi M, Kato K, Nagafuji K, Ogawa R, Eto T, Iwasaki H, Akashi K.
  • Journal Title: Clinical Lymphoma Myeloma and Leukemia. Volume: 15 Pages: e47-54.
  • DOI: 10.1016/j.clml.2014.09.006.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma. (2015)
  • Author(s): Kako S, Izutsu K, Kato K, Kim SW, Mori T, Fukuda T, Kobayashi N, Taji H, Hashimoto H, Kondo T, Sakamaki H, Morishima Y, Kato K, Suzuki R, Suzumiya J; on behalf of the Adult Lymphoma Working Group of the Japanese Society for Hematopoietic Cell Transplantation.
  • Journal Title: Am J Hematol. Volume: 90 Pages: 132-138
  • DOI: 10.1002/ajh.23897.
  • Peer Reviewed / Open Access
• [Journal Article] High-dose chemotherapy with autologous stem cell transplantation for elderly patients with relapsed/refractory diffuse large B-cell lymphoma: a nationwide retrospective study. Biol Blood Marrow Transplant. (2014)
  • Author(s): Chihara D, Izutsu K, Kondo E, Sakai R, Mizuta S, Yokoyama K, Kaneko H, Kato K, Hasegawa Y, Chou T, Sugahara H, Henzan H, Sakamaki H, Suzuki R, Suzumiya J.
  • Journal Title: Biol Blood Marrow Transplant. Volume: 20 Pages: 684-689
  • DOI: 10.1016/j.bbmt.2014.01.025.
  • Peer Reviewed / Open Access
• [Journal Article] The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell. (2014)
  • Author(s): Shima T, Miyamoto T, Kikushige Y, Yuda J, Tochigi T, Yoshimoto G, Kato K, Takenaka K, Iwasaki H, Mizuno S, Goto N, Akashi K.
  • Journal Title: Exp Hematol. Volume: 42 Pages: 955-965
  • DOI: 10.1016/j.exphem.2014.07.267.
  • Peer Reviewed / Open Access
• [Journal Article] Combination of bortezomib, thalidomide, and dexamethasone (VTD) as a consolidation therapy after autologous stem cell transplantation for symptomatic multiple myeloma in Japanese patients. (2014)
  • Author(s): Takashima S, Miyamoto T, Kadowaki M, Ito Y, Aoki T, Takase K, Shima T, Yoshimoto G, Kato K, Muta T, Shiratsuchi M, Takenaka K, Iwasaki H, Teshima T, Kamimura T, Akashi K.
  • Journal Title: Int J Hematol. Volume: 100 Pages: 159-164
  • DOI: 10.1007/s12185-014-1611-1.
  • Peer Reviewed / Open Access
• [Journal Article] Treatment of Patients with Adult T Cell Leukemia/Lymphoma with Cord Blood Transplantation: A Japanese Nationwide Retrospective Survey. (2014)
  • Author(s): Kato K, Choi I, Wake A, Uike N, Taniguchi S, Moriuchi Y, Miyazaki Y, Nakamae H, Oku E, Murata M, Eto T, Akashi K, Sakamaki H, Kato K, Suzuki R, Yamanaka T, Utsunomiya A.
  • Journal Title: Biol Blood Marrow Transplant. Volume: 20 Pages: 1968-1974
  • DOI: 10.1016/j.bbmt.2014.08.012.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Long-term remission after high-dose chemotherapy followed by auto-SCT as consolidation for intravascular large B-cell lymphoma. (2014)
  • Author(s): Kato K, Ohno Y, Kamimura T, Kusumoto H, Tochigi T, Jinnouchi F, Kohno K, Kuriyama T, Henzan H, Takase K, Kawano I, Kadowaki M, Nawata R, Muta T, Eto T, Iawasaki H, Ohshima K, Miyamoto T, Akashi K.
  • Journal Title: Bone Marrow Transplant. Volume: 49 Pages: 1543-1544
  • DOI: 10.1038/bmt.2014.189.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Graft-Versus-Host Disease Targets Granulosa Cell of Ovarian Follicle and Causes Infertility after Allogeneic Hematopoietic Stem Cell Transplantation (2015)
  • Author(s): Shimoji S, Hashimoto D, Kato K, Tujigiwa H, Akashi K, Teshima T
  • Organizer: 2015 BMT Tandem Meetings
  • Place of Presentation: サンデイエゴ(USA)
  • Year and Date: 2015-02-11 – 2015-02-14
• [Presentation] Risk Stratification of Outcomes Among Patients with Adult T-Cell Leukemia/Lymphoma Receiving Allogeneic Hematopoietic Cell Transplantation: A Retrospective Analysis of the JSHCT ATL Working Group (2015)
  • Author(s): Yoshimitsu M, Tanosaki R, Kato K, Ishida T, Choi I, Fukuda T, Takatsuka Y, Eto T, Uchida N, Moriuchi Y, Nagamura-Inoue T, Mori S, Sakamaki H, Atsuta Y, Utsunomiya A
  • Organizer: 2015 BMT Tandem Meetings
  • Place of Presentation: サンデイエゴ(USA)
  • Year and Date: 2015-02-11 – 2015-02-14
• [Presentation] Second Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) for Relapse of Hematological Malignancies after First Allo-HSCT (2014)
  • Author(s): Kato K, Miyamoto T, Yonemoto K, Uchida N, Ogawa H, Fukuda T, Takahashi S, Ohashi K, Eto T, Nagamura-Inoue T, Sakamaki H, Morishima Y, Suzuki R, Atsuta Y, Akashi K
  • Organizer: 第56回アメリカ血液学会年次集会
  • Place of Presentation: サンフランシスコ(USA)
  • Year and Date: 2014-12-05 – 2014-12-09
• [Presentation] High-dose chemotherapy followed by auto-PBSCT for intravascular large B-cell lymphoma(IVLBCL) (2014)
  • Author(s): Kato K, Mori T, Kim S, Sawa M, Sakai T, Hashimoto H, Taguchi J, Tanaka J, Nagamura-Inoue T, morishima Y, Suzuki R, Suzumiya J.
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Graft-Versus-Host Disease targets ovary and causes infertilith after allo-HSCT (2014)
  • Author(s): Shimoji S, Kato K, Tujigawa H, Eriguchi Y, Uryu H, Takashima S, Hashimoto D, Miyamoto T, Uwasaki H, Akashi K, Teshima T.
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] 悪性リンパ腫の治療の現況 (2014)
  • Author(s): 加藤光次
  • Organizer: 第12回日本臨床腫瘍学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2014-07-18 – 2014-07-18
  • Invited
• [Presentation] 成人T細胞性白血病/リンパ腫の治療の現在、そして未来 (2014)
  • Author(s): 加藤光次
  • Organizer: 第54回日本網内系学会総会
  • Place of Presentation: 山形
  • Year and Date: 2014-06-21 – 2014-06-21
  • Invited
• [Book] ファーマナビゲーターDIC編 (2014)
  • Author(s): 加藤光次、丸山征郎
  • Total Pages: 8
  • Publisher: メディカルレビュー社