Research Projects

2006 - 2007

Analysis of the innate immune responses in the liver of patients with chronic hepatitis C following liver transplantation to develop a novel immunotherapy for the recurrent hepatitis C infection

Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

Grant number
18590723
Japan Grant Number (JGN)
JP18590723
Grant amount
(Total)
3,920,000 Japanese Yen
(Direct funding)
3,500,000 Japanese Yen
(Indirect funding)
420,000 Japanese Yen
Grant type
Competitive

(1) Natural killer (NK) cell subsets in the liver of patients with recurrent hepatitis C following liver transplantation
Human NK cells can be divided into two subsets based on their cell-surface density of CD56 - CD56^(+bright) and CD56^(+dim) - each with distinct phenotypic properties. We investigated the NK cell subsets in the liver of patients with recurrent hepatitis C following living-donor liver transplantation (LDLT). The patients with chronic hepatitis C (CHC) and the donors for LDLT were also investigated as controls. We revealed that the CD56^(+bright) subset was significantly decreased in the liver of patients with recurrent hepatitis C than that in the patients with CHC and the normal donors. The expression of an activation marker CD69 on the CD56^(+dim) subset was significantly increased in the liver of LDLT. Our results suggest that further examination of the status of intrahepatic NK cell subsets might provide a new insight into the mechanism of rapid progression of recurrent hepatitis C infection.
(2) Gene expression profiles in the liver of patients with recurrent hepatitis C following liver transplantation
We investigated the gene expression profiles in the liver of patients with recurrent hepatitis C after LDLT using liver biopsy samples. However, we could not find any significant changes in the gene expression profiles among the recurrent hepatitis C patients and CHC patients yet.
(3) NK and NKT cells in the liver of patients with chronic hepatitis C before and after interferon plus ribavirin therapy
Previous studies have revealed that functional impairment of NK and NKT cells might be associated with the persistence of hepatitis C virus (HCV). However, the involvement of these cells, which predominate in the liver, in therapeutic HCV clearance is still unclear. We found a close relationship between the significant increase of intrahepatic NK/NKT cells and sustained HCV clearance in CHC patients treated with interferon-a plus ribavirin therapy.

Link information
KAKEN
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590723
ID information
  • Grant number : 18590723
  • Japan Grant Number (JGN) : JP18590723