Significance of CD8-positive T lymphocytes in graft and recipient peripheral blood in the immunoresponse after allogeneic cord blood transplantation

• Project/Area Number: 20591149
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Nagoya University
• Principal Investigator: MURATA Makoto Nagoya University, 医学部附属病院, 講師 (40378063)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Haruhiko 名古屋大学, 大学院・医学系研究科, 准教授 (90283431)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 臍帯血移植 / 骨髄移植 / 生着 / 拒絶 / 移植片対宿主病 / 移植片対白血病効果 / T細胞 / HLA / CD8 / CD4

Research Abstract

We analyzed a significance of CD8-positive T lymphocytes in graft and recipient peripheral blood in the immunoresponse after allogeneic hematopoietic stem cell transplantation. We observed the followings : (1) recovery of nalve CD8-positive T lymphocytes after cord blood transplantation is comparable to that after bone marrow transplantation, (2) CD8-positive T lymphocytes that survive beyond pre-transplant conditioning can cause graft rejection, and (3) under immunological pressure by CD8-positive T lymphocytes that recognize mismatched HLA molecule between donor and recipient, residual leukemia blast clones whose HLA expression is low can expand and result in relapse.

Research Products

• [Journal Article] Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT. (2011)
  • Author(s): Murase M, Nishida T, Onizuka M, Inamoto Y, Sugimoto K, Imahashi N, Murata M, Miyamura K, Kodera Y, Inoko H, Naoe T.
  • Journal Title: Bone Marrow Transplantation 印刷中
  • Peer Reviewed
• [Journal Article] A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies. (2011)
  • Author(s): Terakura S, Atsuta Y, Sawa M, Ohashi H, Kato T, Nishiwaki S, Imahashi N, Yasuda T, Murata M, Miyamura K, Suzuki R, Naoe T, Ito T, Morishita Y.
  • Journal Title: Annals of Oncology 印刷中
  • Peer Reviewed
• [Journal Article] Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT. (2011)
  • Author(s): Murase, M, et al.
  • Journal Title: Bone Marrow Transplantation Volume: 印刷中(未定) Pages: 2011-2011
  • Peer Reviewed
• [Journal Article] A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrowtransplantation from unrelated donors in patients with hematopoietic malignancies. (2011)
  • Author(s): Terakura S, et al.
  • Journal Title: Annals of Oncology Volume: 印刷中(未定) Pages: 2011-2011
  • Peer Reviewed
• [Journal Article] Donor single nucleotide polymorphism in the CCR9 gene affects the incidence of skin GVHD. (2010)
  • Author(s): Inamoto Y, Murata M, Katsumi A, Kuwatsuka Y, Tsujimura A, Ishikawa Y, Sugimoto K, Onizuka M, Terakura S, Nishida T, Kanie T, Taji H, Iida H, Suzuki R, Abe A, Kiyoi H, Matsushita T, Miyamura K, Kodera Y, Naoe T.
  • Journal Title: Bone Marrow Transplantation 45 Pages: 363-369
  • Peer Reviewed
• [Journal Article] Donor single nucleotide polymorphism in the CCR9 gene affects the incidence of skin GVHD (2010)
  • Author(s): Inamoto Y, et al.
  • Journal Title: Bone Marrow Transplantation 45 Pages: 363-369
  • Peer Reviewed
• [Journal Article] Cytotoxic T lymphocyte clones isolated from an HLA-Cw-mismatched bone marrow transplant recipient with acute graft-versus-host disease. (2009)
  • Author(s): Sugimoto K, Murata M, Terakura S, Naoe T.
  • Journal Title: Journal of Immunology 183 Pages: 5991-5998
  • Peer Reviewed
• [Journal Article] Irrespective of CD34 expression, lineage- committed cell fraction reconstitutes and reestablishes transformed Philadelphia chromosome-positive leukemia in NOG mice. (2009)
  • Author(s): Tanizaki R, Nomura Y, Miyata Y, Minami Y, Abe A, Hanamura A, Sawa M, Murata M, Kiyoi H, Matsushita T, Naoe T.
  • Journal Title: Cancer Science 101(3) Pages: 631-638
  • Peer Reviewed
• [Journal Article] Clinicopathological manifestations and treatment of intestinal transplant-associated microangiopathy (i-TAM). (2009)
  • Author(s): Inamoto Y, Ito M, Suzuki R, Nishida T, Iida H, Kohno A, Sawa M, Murata M, Nishiwaki S, Oba T, Yanada M, Naoe T, Ichihashi R, Fujino M, Yamaguchi T, Morishita Y, Hirabayashi N, Kodera Y, Miyamura K.
  • Journal Title: Bone Marrow Transplantation 44 Pages: 43-49
  • Peer Reviewed
• [Journal Article] Clinicopathological manifestations and treatment of intestinal transplant-associated microangiopathy(i-TAM) (2009)
  • Author(s): Inamoto Y, et al.
  • Journal Title: Bone Marrow Transplantation 44 Pages: 43-49
  • Peer Reviewed
• [Journal Article] Cytotoxic T lymphocyte clones isolated from an HLA-Cw-mismatched bonemarrow transplant recipient with acute graft-versus-host disease (2009)
  • Author(s): Sugimoto K, et al.
  • Journal Title: Journal of Immunology 183 Pages: 5991-5998
  • Peer Reviewed
• [Journal Article] Potential role of a mismatched HLA-specific CTL clone developed pretransplant in graft rejection following cord blood transplantation. (2008)
  • Author(s): Narimatsu H, Murata M, Terakura S, Sugimoto K, Naoe T.
  • Journal Title: Biology of Blood and Marrow Transplantation 14 Pages: 397-402
  • Peer Reviewed
• [Journal Article] Donor cell leukemia after allogeneic peripheral blood stem cell transplantation : a case report and literature review. (2008)
  • Author(s): Murata M, Ishikawa Y, Ohashi H, Terakura S, Ozeki K, Kiyoi H, Naoe T.
  • Journal Title: International Journal of Hematology 88 Pages: 111-115
  • NAID: 10025159310
  • Peer Reviewed
• [Journal Article] Clinical characteristics of chronic graft-versus-host disease following umbilical cord blood transplantation for adults (2008)
  • Author(s): Sugimoto K, et al.
  • Journal Title: Bone Marrow Transplantation 41 Pages: 729-736
  • Peer Reviewed
• [Journal Article] High incidence of graft failure in unrelated cord blood transplantation using a reduced intensity preparative regimen consisting of fludarabine and melphalan (2008)
  • Author(s): Narimatsu H, et al.
  • Journal Title: Bone Marrow Transplantation 41 Pages: 753-756
  • Peer Reviewed
• [Journal Article] Decreased Risk of Acute Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with the 5, 10-Methy lenetetrahydrofolate Reductase 677TT Genotype (2008)
  • Author(s): Sugimoto K, et al.
  • Journal Title: International Journal of Hematology 87 Pages: 451-458
  • Peer Reviewed
• [Journal Article] Potential role of a mismatched HLA-specific CTL clone developed. pretransplant in graft rejection following cord blood transplantation (2008)
  • Author(s): Narimatsu H, et al.
  • Journal Title: Biology of Blood and Marrow Transplantation 14 Pages: 397-402
  • Peer Reviewed
• [Journal Article] Donor Cell Leukemia after Allogeneic Peripheral Blood Stem Cell Transplantation : A Case Report and Literature Review (2008)
  • Author(s): Murata M, et al.
  • Journal Title: International Journal of Hematology 88 Pages: 111-115
  • NAID: 10025159310
  • Peer Reviewed
• [Journal Article] Retension but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy (2008)
  • Author(s): Abe A, et al.
  • Journal Title: International Journal of Hematology 88 Pages: 471-475
  • Peer Reviewed
• [Presentation] Exhaustion of CMV specific T cells with enhanced PD-1 expression in persistent cytomegalovirus infection after allogeneic stem cell transplantation. (2010)
  • Author(s): Kato T, Murase M, Daikoku T, Shiraki K, Murata M, Naoe T
  • Organizer: The 52nd Annual Meeting of the American Society of Hematology
  • Place of Presentation: Orange County Convention Center(フロリダ州オーランド)
  • Year and Date: 2010-12-06
• [Presentation] Exhaustion of CMV specific T cells with enhanced PD-1 expression in persistentcytomegalovirus infection after allogeneic stem cell transplantation. (2010)
  • Author(s): Kato T, et al.
  • Organizer: The 52nd Annual Meeting of the American Society of Hematology
  • Place of Presentation: Orange County Convention Center(フロリダ州オーランド)
  • Year and Date: 2010-12-06
• [Presentation] Mechanism of persistent cytomegalovirus infection after allogeneic stem cell transplantation. (2010)
  • Author(s): Kato T, Nishida T, Murase M, Daikoku T, Shiraki K, Murata M, Naoe T
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-24
• [Presentation] Generation of CMV antigen specific CTL using closed culture system. (2010)
  • Author(s): Nishida T, et al.
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-24
• [Presentation] 教育講演3:造血幹細胞移植 (2010)
  • Author(s): 村田誠
  • Organizer: 第19回日本組織適合性学会大会
  • Place of Presentation: 東京大学(東京都)
  • Year and Date: 2010-09-19
• [Presentation] 教育講演3:造血幹細胞移植. (2010)
  • Author(s): 村田誠
  • Organizer: 第19回日本組織適合性学会大会
  • Place of Presentation: 東京大学(東京都)
  • Year and Date: 2010-09-19
• [Presentation] 同種造血幹細胞移植におけるCytotoxic T-Lymphocyte Antigen 4(CTLA-4)遺伝子多型の影響 (2010)
  • Author(s): 村瀬未帆、西田徹也、鬼塚真仁、稲本賢弘、杉本恭子、今橋伸彦、村田誠、宮村耕一、小寺良尚、猪子英俊、直江知樹
  • Organizer: 第32回日本造血細胞移植学会総会
  • Place of Presentation: 浜松アクトシティ(静岡県)
  • Year and Date: 2010-02-19
• [Presentation] Optimization of fludarabine + melphalan conditioning for marrow transplantation from unrelated donors for patients with hematopoietic malignancies : a prospective dose-finding trial using modified continual reassessment method. (2009)
  • Author(s): Terakura S, Sawa M, Ohashi H, Kato T, Nishiwaki S, Imahashi N, Murata M, Miyamura K, Atsuta Y, Suzuki R, Naoe T, Ito T, Morishita Y.
  • Organizer: The 51st Annual Meeting of the American Society of Hematology
  • Place of Presentation: New Orleans Convention Center(ルイジアナ州ニューオーリンズ)
  • Year and Date: 2009-12-06
• [Presentation] Optimization of fludarabine+melphalan conditioning for marrow transplantation from unrelated donors for patients with hematopoietic malignancies : a prospective dose-finding trial using modified continual reassessment method (2009)
  • Author(s): Terakura S, et al.
  • Organizer: The 51th annual meeting of the American Society of Hematology
  • Place of Presentation: ニューオーリンズ、米国
  • Year and Date: 2009-12-06
• [Presentation] 日本臍帯血バンクネットワーク.原発性骨髄線維症に対する臍帯血移植 (2009)
  • Author(s): 村田誠, 谷口修一, 長村-井上登紀子, 加藤剛二
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2009-10-25
• [Presentation] Characteristics of CTL clones isolated from bone marrow transplant recipient with HLA-Cw-mismatched donor. (2009)
  • Author(s): Murata M, Sugimoto K, Terakura S, Naoe T
  • Organizer: 2009 BMT Tandem Meetings
  • Place of Presentation: Tampa Convention Center(フロリダ州タンパ)
  • Year and Date: 2009-02-15
• [Presentation] Clinicopathological manifestations and treatment of intestinal transplant-associated microangiopathy (I-TAM). (2009)
  • Author(s): Inamoto Y, et al.
  • Organizer: 2009 BMT Tandem Meetings
  • Place of Presentation: タンパ、米国
  • Year and Date: 2009-02-15
• [Presentation] Characteristics of CTL clones isolated from bone marrow transplant recipient with HLA-Cw-mismatched donor (2009)
  • Author(s): Murata M, et al.
  • Organizer: 2009 BMT Tandem Meetings
  • Place of Presentation: タンパ、米国
  • Year and Date: 2009-02-15
• [Presentation] シンポジウム3骨髄内臍帯血移植 (2009)
  • Author(s): 村田誠
  • Organizer: 第31回日本造血細胞移植学会総会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2009-02-06
• [Presentation] 骨髄内臍帯血移植 (2009)
  • Author(s): 村田誠, 他
  • Organizer: 第31回日本造血細胞移植学会総会
  • Place of Presentation: 札幌市
  • Year and Date: 2009-02-06
• [Presentation] 深在性真菌症を有する患者に対する新規抗真菌在を併用した同種造血幹細胞移植 (2009)
  • Author(s): 柳澤真弓, 他
  • Organizer: 第31回日本造血細胞移植学会総会
  • Place of Presentation: 札幌市
  • Year and Date: 2009-02-05
• [Presentation] Retention but Significant Reduction of BCR-ABL Transcript in Hemato poietic Stem Cells in Chronic Myelogenous Leukemia after Imatinib Therapy (2008)
  • Author(s): Abe A, et al.
  • Organizer: The 50th annual meeting of the American Society ofHematology
  • Place of Presentation: サンフランシスコ、米国
  • Year and Date: 2008-12-07
• [Presentation] Characterization of cytotoxic T lymphocyte clones isolated from bone marrow transplant recipient with HLA-Cw-mismatched donor. (2008)
  • Author(s): Sugimoto K, Murata M, Terakura S, Naoe T
  • Organizer: The 50th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Moscone Center(カリフォルニア州サンフランシスコ)
  • Year and Date: 2008-12-06
• [Presentation] Donor Single Nucleotide Polymorphism in the CCR9 Gene Affects the Incidence of Acute Skin Graft-Versus-Host Disease (2008)
  • Author(s): Inamoto Y, et al.
  • Organizer: The 50th annual meeting of the American Society of Hematology
  • Place of Presentation: サンフランシスコ、米国
  • Year and Date: 2008-12-06
• [Presentation] Characterization of Cytotoxic T Lymphocyte Clones Isolated from Bone Marrow Transplant Recipient with HLA-Cw-Mismatched Donor (2008)
  • Author(s): Sugimoto K, et al.
  • Organizer: The 50th annual meeting of the American Society of Hematology
  • Place of Presentation: サンフランシスコ、米国
  • Year and Date: 2008-12-06
• [Presentation] 不適合HLA-Cw分子を認識する細胞傷害性T細胞(CTL)クローン (2008)
  • Author(s): 杉本恭子, 他
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-11
• [Presentation] 小腸特異的ケモカイン受容体遺伝子CCR9の一塩基多型は皮膚急性GVHD発症と相関する (2008)
  • Author(s): 稲本賢弘, 他
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-11
• [Presentation] 成人血液悪性疾患に対する減量強度前治療を用いた骨髄内臍帯血移植法の有効性に関する研究 (2008)
  • Author(s): 村田誠, 稲本賢弘, 寺倉精太郎, 鈴木律朗, 小寺良尚, 直江知樹
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2008-10-10
• [Presentation] 成人血液悪性疾患に対する減量強度前治療を用いた骨髄内臍帯血移植法の有効性に関する研究 (2008)
  • Author(s): 村田誠, 他
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-10
• [Book] 診療ガイドラインUP-TO-DATE (2010)
  • Author(s): 村田誠, 直江知樹
  • Publisher: メディカルレビュー社
• [Book] 診療ガイドラインUP-TO-DATE (2010)
  • Author(s): 村田誠, 他
  • Publisher: メディカルレビュー社
• [Remarks] ホームページ等
  • URL: http://www.med.nagoya-u.ac.jp/medical/1639/1674/ketsuekishuyounaikagaku.html
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/medical/1639/1674/ketsuekishuyounaikagaku.html