Analyses of immune tolerance mechanism in allogeneic transplantation
| Project/Area Number |
15K09493
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 骨髄移植 / 制御性T細胞 / 移植片対宿主病 / TNFRSF25 / 造血幹細胞ニッチ |
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| Outline of Final Research Achievements |
Regulatory T cells (Treg) regulate the immune system and enhance immune tolerance after transplantation. In this study, we demonstrated that a single treatment of the agonistic antibody to DR3 to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD. Further, we comprehensively analyzed the immunophenotype of Treg after DR3 signal activation, demonstrating that DR3 activated Treg had an activated/mature phenotype. However, DR3 activation in mice with ongoing GVHD further promoted donor T cell activation/proliferation. These data suggest that the function of DR3 signaling was highly dependent on the activation status of the T cells. Our data demonstrated that DR3 signaling affects the function of Treg and T cell activation after alloantigen exposure in a time-dependent manner.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Foxp3+ regulatory T cells maintain the bone marrow microenvironment for B cell lymphopoiesis.2017
Author(s)
Pierini A, Nishikii H, Baker J, Kimura T, Kwon HS, Pan Y, Chen Y, Alvarez M, Strober W, Velardi A, Shizuru JA, Wu JY, Chiba S, Negrin RS.
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Journal Title
Nature Communications.
Volume: 8
Issue: 1
Pages: 15068-15068
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.2017
Author(s)
Ronald JA, Kim BS, Gowrishankar G, Namavari M, Alam IS, D'Souza, Nishikii H, Chuang HY, Ilovich O, Lin CF, Reeves R, Shuhendler A, Hoehne A, Chan CT, Baker J, Yaghoubi SS, VanBrocklin HF, Hawkins R, Franc BL, Jivan S, Slater JB, Verdin EF, Gao KT, Benjamin J, Negrin R, Gambhir SS.
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Journal Title
Cancer Research
Volume: 77(11)
Issue: 11
Pages: 2893-2902
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Engraftment of Embryonic Stem Cells and Differentiated Progeny by Host Conditioning with Total Lymphoid Irradiation and Regulatory T Cells.2015
Author(s)
Pan Y, Leverson-Gower DB, De Almeida PE, Pierini A, Baker J, Florek M, Nishikii H, Kim BS, Ke R, Wu JC, Negrin RS
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Journal Title
Cell Reports
Volume: 10
Pages: 1793-1802
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Expanded CD4+Foxp3+ regulatory T cells through DR3 signaling showed distinct immunophenotype and prevented the lethal acute-graft and host disease after allogeneic transplantation.2015
Author(s)
Hidekazu Nishikii, Byung Su Kim, Antonio Pierini, Jeanette Baker, Yasuhisa Yokoyama, Dominik Schneidawind, Yuqiong Pan, Maite Alvarez, Yan Chen, Shigeru Chiba, Robert S. Negrin
Organizer
ASH annual meeting 2015
Place of Presentation
米国 オーランド
Year and Date
2015-12-05
Related Report
Int'l Joint Research
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