| Project/Area Number |
15390236
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Aichi Medical University School of Medicine |
|---|
Principal Investigator |
KAKUMU Shinichi Aichi Medical University School of Medicine, Department of Medicine, Professor, 医学部, 教授 (10115545)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Tetsuya Aichi Medical University School of Medicine, Department of Medicine, Lecturer, 医学部, 講師 (10288508)
OKUMURA Akihiko Aichi Medical University School of Medicine, Department of Medicine, Lecturer, 医学部, 講師 (70288512)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥7,600,000 (Direct Cost: ¥7,600,000)
|
|---|
| Keywords | virus hepatitis / hepatocellular carcinoma / NKT cell / α galactosylceramide / peripheral blood mononucler cell / intrahpepatic mononuclear cell / cytokine / CTL / ウイルス性肝炎 / α GalCer / CTL / マウスモデル / Vα14 NKT knockouut mouse / C型肝炎 / 肝臓癌 / T細胞受容体 / Vα24+T細胞 |
|---|
| Research Abstract |
Natural killer T (NKT) cells share features of both classical T cells and NK cells. NKT cells are heterogenous populations, and recognize glycolipids associated with CD1d molecule. We investigated Th1/Th2 cytokine production as well as frequency and phenotype of circulating NKT cells in patients with chronic hepatitis (CH) and hepatocellular carcinoma (HCC) infected with hepatitis C virus (HCV). Peripheral blood mononuclear cells (PBMC) were obtained befor and 2 weeks later IFN/ribavirin and radiofrequency ablation therapy for CH and HCC, respectively. PBMC were cultured with α galactosylceramide (α GalCer) and IL-2. Frequency and cytokine production of NKT cells were analyzed with flow cytometry. IFN-γ production of Vα 24+CD3+ T cells did not differ among groups, but became greater after treatment in contrast to lowered IL-4 production.
The function of dendritic cells (DCs) appears to be decreased in patients with chronic hepatitis C. However, we have no strategy to modulate its functi
… More
on. Thus we wanted to induce maturated DC by activating V α 24+ NKT cells. We cultured peripheral blood CD14+ cells in the presence of GMCSF and IL-4. Simultaneously CD3+ T cells were cultured with α GalCer + IL-2. After 5-day culture, they are mixed and cultured with GMCSF, α GalCer and IL-2 for further 2 days. This method induced matured, functional DC.
Cytotoxic T lymphocyes (CTLs) are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus (HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. We found that α GalCer, a ligand for V α 14+ NKT cells in mice, strongly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HbsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HbsAg or α GalCer alone failed to HbsAg-specific CTLs, but they were induced by administration of both compounds. A blocking experiment using antibodies to cytokines and CD4O ligand showed that IL-2 mediates the enhancement of CTL induction caused by α GalCer through NKT activation. Less
|
