2010 Fiscal Year Final Research Report
Development of novel cellular therapy for T cell mediated rejection via direct and indirect pathway using regulatory liver sinusoidal endothelial cells (LSEC) in transplantation
| Project/Area Number |
21890155
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Hiroshima University |
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Principal Investigator |
ONOE Takashi Hiroshima University, 病院, 病院助教 (90549809)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 肝移植 / 免疫寛容 / 移植免疫 / 類洞内皮細胞 / キメラ / PD-L1 |
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| Research Abstract |
We have shown that liver sinusoidal endothelial cells (LSEC) has antigen specific immune-suppressive potential in vitro. In this study, we evaluated the possibility that adoptive transfer of isolated allogeneic LSECs induce immune-tolerance in vivo mouse model. Allogeneic BALB/cA LSECs were intraportally injected into immunodeficient RAG2/gc double-knockout (DKO) mice. After orthotopic allogeneic LSEC engraftment, engrafted LSECs expressed PD-L1 molecule. DKO mice were immune-reconstituted using C57BL/6 syngeneic splenocytes. After immune reconstitution, mixed lymphocyte reaction revealed specific inhibition of host alloreactive T-cell proliferation. Furthermore, allogeneic LSEC engraftment significantly prolonged subsequently grafted cognate allogeneic heart survival in DKO mice immune-reconstituted with syngeneic bone marrow transplantation. In conclusion, murine LSECs are capable of suppressing T cells with specificity cognate to LSECs in an in vivo model.
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