The new development of treatment for graft-versus-host disease through memory T cells
Project/Area Number |
22591063
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
|
Research Institution | Kyushu University |
Principal Investigator |
KATO Koji 九州大学, 大学病院・血液腫瘍内科, 助教 (20571764)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 造血幹細胞移植学 / GVHD / メモリーT細胞 / メモリー細胞 / ポリコーム遺伝子 |
Research Abstract |
Histone methylation is thought to be important for regulating antigen-driven T cell responses. However,little is known about the impact of modulating histone methylation on inflammatory T cell responses.We demonstrate that in vivo administration of the histone methylation inhibitor 3-deazaneplanocin A (DZNep) arrests ongoing graft-versus-host disease(GVHD)in mice after alloge neic bone marrow transplantation (BMT).DZNep caused selective apoptosis in alloantigen-activated T cells mediating host tissue injury.This effect was associated with DZNep's ability to selectively reduce trimethylation of histone H3 lysine 27 (H3K27me3), deplete the histone methyltransferase Ezh2 specific to H3K27me3 and activate pro-apoptotic gene Bim repressed by Ezh2 in antigenic-activated T cells. In contrast, DZNep did not impact the survival of alloantigen-unresponsive T cells in vivo and naive T cells stimulated by IL-2 or IL-7 in vitro. Importantly, inhibition of histone methylation by DZNep treatment in vivo preserved the anti-leukemia activity of donor T cells and did not impair the recovery of hematopoiesis and lymphocytes, leading to significantly improved survival of recipients after allogeneic BMT.Our findings indicate that modulation of histone methylation may have significant implications in the development of novel approaches to treat ongoing GVHD and other T cell-mediated inflammatory disorders in a broad context.
|
Report
(4 results)
Research Products
(83 results)
-
[Journal Article] Diffuse panbronchiolitis after humanized anti-CCR4 monoclonal antibody therapy for relapsed adult T-cell leukemia/lymphoma.2013
Author(s)
Kato K, Miyamoto T, Numata A, Nakaike T, Oka H, Yurino A, Kuriyama T, Mori Y, Yamasaki S, Muta T, Takenaka K, Iwasaki H, Teshima T, Akashi K.
-
Journal Title
Int J Hematol.
Volume: 97
Pages: 430-2
DOI
Related Report
Peer Reviewed
-
[Journal Article] nhibition of histone methylation arrests ongoing graft-versus-host disease in mice by selectively inducing apoptosis of alloreactive effector T cells.2012
Author(s)
He S*, Wang J*, Kato K*, Xie F, Varambally S, Mineishi S, Kuick R, Mochizuki K, Liu Y, Nieves E, Mani RS, Chinnaiyan AM, Marquez VE, Zhang Y (*Equal contribution to this work)
-
Journal Title
IBlood.
Volume: 119
Pages: 1274-82
DOI
Related Report
Peer Reviewed
-
[Journal Article] Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study.2012
Author(s)
Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Taniguchi S, Eto T, Takatsuka Y, Miyazaki Y, Moriuchi Y, Hidaka M, Akashi K, Uike N, Sakamaki H, Morishima Y, Kato K, Suzuki R, Nishiyama T, Utsunomiya A.
-
Journal Title
Blood.
Volume: 120
Pages: 1734-41
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Initial low-dose valganciclovir as a preemptive therapy is effective for cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients.2012
Author(s)
Takenaka K, Nagafuji K, Takase K, Kamimura T, Mori Y, Ito Y, Nishi Y, Henzan H, Kato K, Harada N, Eto T, Miyamoto T, Teshima T, Akashi K.
-
Journal Title
Int J Hematol
Volume: 96
Pages: 94-100
DOI
Related Report
Peer Reviewed
-
[Journal Article] Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation.2012
Author(s)
Mori Y, Miyamoto T, Kato K, Kamezaki K, Kuriyama T, Oku S, Takenaka K, Iwasaki H, Harada N, Shiratsuchi M, Abe Y, Nagafuji K, Teshima T, Akashi K.
-
Journal Title
Biol Blood Marrow Transplant.
Volume: 18
Pages: 458-65
DOI
Related Report
Peer Reviewed
-
[Journal Article] Low incidence of adenovirus hemorrhagic cystitis following autologous hematopoietic stem cell transplantation in the rituximab era.2012
Author(s)
Mori Y, Miyamoto T, Kamezaki K, Kato K, Kikushige Y, Takashima S, Urata S, Shimoda S, Shimono N, Takenaka K, Iwasaki H, Nagafuji K, Teshima T, Akashi K.
-
Journal Title
Am J Hematol.
Volume: 87
Pages: 828-30
DOI
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Inhibition of histone methylation arrests ongoing graft-versus-host disease in mice by selectively inducing apoptosis of alloreactive effector T cells2012
Author(s)
He S*, Wang J*, Kato K*, Xie F, Varambally S, Mineishi S, Kuick R, Mochizuki K, Liu Y, Nieves E, Mani RS, Chinnaiyan AM, Marquez VE, Zhang Y.(*Equal contribution to this work)
-
Journal Title
Blood
Volume: 119
Pages: 1274-1282
DOI
Related Report
Peer Reviewed
-
[Journal Article] Notch signaling is a critical regulator of allogeneic CD4+ T cell responses mediating graft-versus-host disease.2011
Author(s)
Zhang Y, Sandy AR, Wang J, Radojcic V, Shan GT, Tran IT, Friedman A, Kato K, He S, Cui S, Hexner E, Frank DM, Emerson SG, Pear WS, Maillard I.
-
Journal Title
Blood.
Volume: 117
Pages: 299-308
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
[Journal Article] for the Fukuoka Blood and Marrow Transplantation Group. ,Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group.2010
Author(s)
Numata A, Miyamoto T, Ohno Y, Kamimura T, Kamezaki K, Tanimoto T, Takase K, Henzan H, Kato K, Takenaka K, Fukuda T, Harada N, Nagafuji K, Teshima T, Akashi K, Harada M and Eto T
-
Journal Title
Bone Marrow Transplant.
Volume: 45
Pages: 311-6
DOI
Related Report
Peer Reviewed
-
[Journal Article] High incidence of HHV6-associated encephalitis/myelitis following a second unrelated cord blood transplantation.2010
Author(s)
Mori Y, Miyamoto T, Nagafuji K, Kamezaki K, Yamamoto A, Saito N, Kato K, Takenaka K, Iwasaki H, Harada N, Abe Y, Teshima T, Akashi K.
-
Journal Title
Biol Blood Marrow Transplant.
Volume: 16
Pages: 1596-1602
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Inhibition of histone methylation arrests ongoing graft-versus-host disease in mice by selectively inducing apoptosis of alloreactive effector T cells2011
Author(s)
He S, Wang J, Kato K, Xie F, Varambally S, Mineishi S, Kuick R, Mochizuki K, Liu Y, Nieves E, Mani RS, Chinnaiyan AM, Marquez VE, Zhang Y
Organizer
53rd Annual Meeting of the American Society of Hematology
Place of Presentation
米国、サンフランシスコ
Year and Date
2011-12-12
Related Report
-
[Presentation] A prospective feasibility trial of unrelated bone marrow transplantation with reduced intensity conditioning regimen for elderly patients with adult T-cell leukemia/lymphoma (ATL)2011
Author(s)
Eto T, Choi I, Tanosaki R, Takatsuka Y, Utsunomiya A, Takemoto S, Taguchi J, Fukushima T, Kato K, Teshima T, Suehiro Y, Yamanaka T, Okamura J, Uike N
Organizer
53rd Annual Meeting of the American Society of Hematology
Place of Presentation
米国、サンフランシスコ
Year and Date
2011-12-12
Related Report
-
-
-
[Presentation] 同種骨髄移植ドナーよりEBV初感染を来した一例2011
Author(s)
林正康, 菊繁吉謙, 加藤光次, 湯田淳一朗, 浦田真吾, 高嶋秀一郎, 竹中克斗, 谷本一樹, 岩崎浩己, 宮本敏浩, 豊嶋崇徳, 赤司浩一
Organizer
第16回九州骨髄移植カンファレンス
Place of Presentation
福岡
Year and Date
2011-11-05
Related Report
-
-
-
[Presentation] Preemptive therapy for cytomegalovirus infection by low dose valganciclovir after allogeneic HSCT2011
Author(s)
Takenaka K, Nagafuji K, Takase K, Kamimura T, Nishi Y, Kato K, Henzan H, Ito Y, Harada N, Miyamoto T, Eto T, Akashi K, Teshima T
Organizer
第73回日本血液学会学術総会
Place of Presentation
名古屋
Year and Date
2011-10-15
Related Report
-
[Presentation] BK virus hemorrhagic cystitis in allo-HSCT : Is seasonal distribution caused by nosocomial infection?2011
Author(s)
Kato K, Miyamoto T, Oku S, Kuriyama T, Mori Y, Takenaka K, Harada N, Iwasaki H, Murata M, Furusho N, Shimono N, Teshima T, Hayashi J, Akashi K
Organizer
第73回日本血液学会学術総会
Place of Presentation
名古屋
Year and Date
2011-10-15
Related Report
-
[Presentation] Successful reduced-intensity cord blood transplantation for advanced mycosis fungoides2011
Author(s)
Nakaike N, Oku S, Kato K, Sakamoto K, Shimoji S, Kuriyama K, Mori Y, TakenakaK, Kuroiwa M, Harada N, Iwasaki H, Miyamoto T, Teshima T, Oshima K, Akashi K
Organizer
第73回日本血液学会学術総会
Place of Presentation
名古屋
Year and Date
2011-10-15
Related Report
-
[Presentation] 造血幹細胞移植で長期病勢コントロールが得られた腸管症関連T細胞リンパ腫2011
Author(s)
下地園子, 奥誠道, 河野健太郎, 竹中克斗, 栗山拓郎, 加藤光次, 宮本敏浩, 原田直樹, 岩崎浩己, 豊嶋崇徳, 赤司浩一
Organizer
第73回日本血液学会学術総会
Place of Presentation
名古屋
Year and Date
2011-10-15
Related Report
-
-
-
-
[Presentation] Clinical impact of reduced intensity stem-cell transplantation for ATL2011
Author(s)
Ishida T, Hishizawa M, Kato K, Tanosaki R, Eto T, Miyazaki Y, Hidaka M, Sakamaki H, Morishima Y, Suzuki R, Utsunomiya A
Organizer
第73回日本血液学会学術総会
Place of Presentation
名古屋
Year and Date
2011-10-14
Related Report
-
[Presentation] 福岡BMTグループ(FBMTG)における悪性リンパ腫に対する自己末梢血幹細胞移植2011
Author(s)
平安山英穂, 沼田晃彦, 衛藤徹也, 大野裕樹, 上村智彦, 高瀬謙, 伊藤能清, 加藤光次, 杉尾康浩, 竹中克斗, 宮本敏浩, 原田直樹, 長藤宏司, 豊嶋崇徳, 原田実根, 赤司浩一
Organizer
第73回日本血液学会学術総会
Place of Presentation
名古屋
Year and Date
2011-10-14
Related Report
-
-
-
-
[Presentation] 急性骨髄性白血病の初回寛解導入療法中に粟粒結核を発症し、治療に難渋した一例2011
Author(s)
林正康, 高嶋秀一郎, 加藤光次, 浦田真吾, 菊繁吉謙, 谷本一樹, 竹中克斗, 岩崎浩己, 宮本敏浩, 門脇雅子, 江里口芳裕, 下野信行, 門脇賢典, 岡村精一, 豊嶋崇徳, 赤司浩一
Organizer
第1回日本血液学会九州地方会
Place of Presentation
福岡
Year and Date
2011-09-03
Related Report
-
[Presentation] レナリドマイドで病勢コントロールを行い、安全に移植を行えたPOEMS症候群の一例2011
Author(s)
湯田淳一朗, 菊繁吉謙, 加藤光次, 下地園子, 奥誠道, 谷本一樹, 竹中克斗, 岩崎浩己, 宮本敏浩, 豊嶋崇徳, 赤司浩一
Organizer
第1回日本血液学会九州地方会
Place of Presentation
福岡
Year and Date
2011-09-03
Related Report
-
-
-
-
[Presentation] 小児発症の全身脱毛症が初発症状と考えられた成人診断の毛包向性菌状息肉症2011
Author(s)
仲池隆史, 奥誠道, 加藤光次, 坂本佳治, 下地園子, 栗山拓郎, 森康雄, 竹中克斗, 黒岩三佳, 原田直樹, 岩崎浩己, 宮本敏浩, 豊嶋崇徳, 大島孝一, 赤司浩一
Organizer
第51回日本リンパ網内系学会総会
Place of Presentation
福岡
Year and Date
2011-07-02
Related Report
-
-
-
-
-
-
-
-
-
[Presentation] In vitro enhancing oxidative phosphorylation by rapamycin in proliferative CD8+ T cells during antigenic priming augments the generation of long-lived memory T cells in vivo2010
Author(s)
He S, Kato K, Jiang J, Wahl D, Mineishi S, Cui S, Glick G, Murasko D, Zhang Y.
Organizer
The American Association of Immunologists, Immunology 2010, 97th Annual Meeting
Place of Presentation
ボルチモア、USA
Year and Date
2010-05-09
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-