2005 Fiscal Year Final Research Report Summary
Stem cells of the dendritic cell lineage in the liver : demonstration and analysis
| Project/Area Number |
15390059
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
MATSUNO Kenjiro Dokkyo Univ.Medical School, Anatomy (Macro), Professor, 医学部, 教授 (20094047)
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| Co-Investigator(Kenkyū-buntansha) |
SHI Changde Dokkyo Univ.Med.Sch., Anatomy (Macro), Assistant Professor, 医学部, 助手 (80296152)
UETA Hisashi Dokkyo Univ.Med.Sch., Anatomy (Macro), Assistant Professor, 医学部, 助手 (10364556)
EZAKI Taichi Tokyo Women's Med.Univ., Anatomy Dev.Biol., Professor, 医学部, 教授 (10128259)
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| Project Period (FY) |
2003 – 2005
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| Keywords | liver / dendritic cell / stem cell / liver transplantation / congeneic animal / transmigration / allosensitization / rat |
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| Research Abstract |
1.Soon after the liver transplantation, graft-derived DCs with a very immature phenotype, TcR- Ig- MHCI+ MHCII+ ICAM1+ CD11b- CD11c- αEβ7 integrin- and CD86-, performed a diffuse transmigration through the HEV and splenic marginal sinus of host lymphoid tissues. These DCs clustered with host T cells where a massive host proliferative response started.
2.In addition, MHCII+ Ig- B220+ cells with plasmacytoid DC phenotype and MHCII+ TcR+ cells as well as MHCII- T cells and Ig+ B cells concomitantly transmigrated in a similar fashion as the mice model (ref 3, 7).
3&6.While the bone marrow DC fraction transmigrated to host lymphoid tissues after i.v. transfer, the liver crude DC fraction did not, probably because the isolation procedure including enzymal digestion caused cell injury.
4.The tolerance-inducing regimen, donor-specific transfusion (DST) 7 d before operation completely blocked this transmigration and considerably suppressed the proliferative response of host T cells there. The DST regimen itself induced antibody forming-cell response in the host spleen, leading to donor-specific IgM and IgG_1 cytotoxic alloantibody production. This caused a rapid elimination of migrating donor cells in the blood. Since intragraft T cell apoptosis is reported after the murine liver transplantation, we consider that the intrahepatic sensitization without effector T cell production in the host lymphoid tissues may induce the abortive T cell response. The deletion may exceed the production of alloreactive T cells, resulting in the liver operational tolerance.
5.The donor cells persisted up to 2 years after liver transplantation from the congeneic donor rats. Few of them bore DC phenotype.
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