Development of the new cell therapy for GVHD using tolerogenic dendtiric cells treated by PUVA treatment

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461604
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Department of Clinical Research, National Hospital Organization Kanazawa Medical Center
• Principal Investigator: Maeba Hideaki 独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, その他 (10419335)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 制御性樹状細胞 / PUVA / GVHD

Outline of Final Research Achievements

Bone marrow-derived cultured DCs acquired tolerogenicity by PUVA (psoralen+UVA) treatment in mice. In vitro assays, strong tolerogenicity was observed when adding PUVA-DC even from third party strain into MLR. That is, the PUVA-DC have tolerogenic function in a MHC-independent manner. We showed that cell-to-cell contact was needed to mediate the regulatory effect by transwell experiment. Next, we compared the expression of the IDO, which induces T-cell anergy, by real-time PCR between PUVA-DC and BM-DC. An increase IDO gene transcription level was observed in PUVA-DC about 5 times more than in BM-DC. But adding 1-MT, which is an inhibitor of IDO, had no effects on MLR with PUVA-DC.
We transfused PUVA-DC (Host-type, Donor-type, Third-party-type) in a mouse GVHD model, but the GVHD inhibitory effects were not observed. It was thought the survival of PUVA-DC was insufficient. These data leads us to search for technique to make PUVA-DC to survive after in vivo administration.

Free Research Field

GVHD