2012 Fiscal Year Final Research Report
New treatment strategy for GVHD by infusion of PUVA-treated-tolerogenic-dendritic cells
| Project/Area Number |
23791213
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | 国立病院機構金沢医療センター (2012)
Department of Clinical Research, National Hospital Organization Kanazawa Medical Center (2011) |
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Principal Investigator |
MAEBA Hideaki 国立病院機構金沢医療センター, 臨床研究部小児科, 医師 (10419335)
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| Project Period (FY) |
2011 – 2012
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| Keywords | GVHD / 制御性樹状細胞 / 造血幹細胞移植 / PUVA療法 |
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| Research Abstract |
Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory therapy by exposing isolated white blood cells to photoactive 8-MOP (psoralen) and UVA radiation (PUVA) for refractory acute and chronic graft-versus-host disease (GVHD). We have reported that bone marrow-derived dendritic cells (BM-DCs), which are generated from bone marrow cells plus GM-CSF, acquired tolerogenicity by PUVA-treatment in mice. To clarify the mechanisms of how PUVA-treated DCs induce tolerogenicity in further detail, we compared the expression of the indoleamine 2,3-dioxygenase (IDO), which induces T-cell anergy by tryptophan depletion and by the production of metabolic byproducts collectively known as kynurenines, by real-time PCR between PUVA-DCs and BM-DCs. An increased IDO gene transcription level was observed in PUVA-DCs about 5 times more than in BM-DCs. The question we have to consider next is whether tolerogenic capacity is acquired only in DCs or other lymphocytes subpopulations. To test this, PUVA-treated CD4, CD8, or B220 cells from the same strain of stimulator cells were added into the MLR mixture. MLR was suppressed only when PUVA-DCs were added. Infusion of PUVA-treated DCs could have a great potential to treat lethal acute GVHD in clinical settings.
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