Comprehensive analysis of dysfunctional HCV specific CD8 T cell during persistent HCV infection

Research Project

Project/Area Number	24790720
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Gastroenterology
Research Institution	Keio University
Principal Investigator	Ishibashi Yuka 慶應義塾大学, 医学部, 助教 (60528305)
Research Collaborator	Nobuhiro Nakamoto 慶應義塾大学, 医学部(信濃町), 専任講師 (40383749)
Project Period (FY)	2012-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	C型肝炎ウイルス / T細胞疲弊 / 獲得免疫 / C型肝炎 / CD8 T細胞 / NK細胞 / 免疫寛容 / 腸肝相関 / HCV特異的T細胞 / T細胞の疲弊 / C型慢性肝炎 / CD8T細胞 / NKT細胞 / exhaustion
Outline of Final Research Achievements	Peripheral HCV specific CD8 T cells in patients with chronic HCV infections showed higher expressions of suppressive co-stimulation molecules such as PD-1, CTLA4, and LAG-3 compared with EBV or influenza specific CD8 T cells from the same individuals. HCV specific CD8 T cells in patients with higher viral load tended to express multiple suppressive co-stimulation molecules. Of interest, PD-1 positive HCV specific CD8 T cells produced higher TNFα and lower IL-10 compared with PD-1 negative subsets. There results suggest that HCV specific CD 8 T cells fall to be dysfunctional via the expression of multiple suppressive co-stimulation molecules during persistent HCV infection. Further study is needed to clarify the mechanism behind the immune tolerance in the liver and to overcome the HCV infection in humans.