The role of PD1 pathway on tolerance after allogeneic transplantation

Research Project

Project/Area Number	24591425
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Hematology
Research Institution	Okayama University
Principal Investigator	TANIMOTO Mitsune 岡山大学, 医歯(薬)学総合研究科, 教授 (10240805)
Co-Investigator(Kenkyū-buntansha)	MAEDA Yoshinobu 岡山大学, 岡山大学病院, 講師 (60403474)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	GVHD / ＧＶＨＤ
Outline of Final Research Achievements	The results of this study show that the PD-1 pathway is important in the alleviation of chronic GVHD. Blockade of the PD-1 pathway using anti PD-1, anti PD-L1, or anti PD-L2 mAbs exacerbated chronic GVHD, and chimeric mice showed the importance of PD-L1 expression in host tissues in attenuating chronic GVHD. BMT into PD-L1 deficient recipients revealed IL-17+IFN-gamma+ T cell expansion and Am80 administration of Am80 overcame the IL-17+IFN-gamma+ T cell expansion caused by PD-L1 deficiency, resulting in reduced chronic GVHD damage in PD-L1 deficient recipients. Stimulation of the PD-1 pathway with an agonistic anti PD-1 mAb alleviated chronic GVHD, suggesting a new target for the prevention or treatment of chronic GVHD.