The Function of HCV specific TGF-β-producing helper T cell in chronic hepatitis C patient

Research Project

Project/Area Number	13670550
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Gastroenterology
Research Institution	JICHI MEDICAL SCHOOL
Principal Investigator	NAKAMURA Ikuo Jichi Medical School, Assistant Professor, 医学部, 講師 (40251243)
Co-Investigator(Kenkyū-buntansha)	IMAWARI Michio Showa Univ., School of Medicine, Professor, 医学部, 教授 (70134228)
Project Period (FY)	2001 – 2003
Project Status	Completed (Fiscal Year 2003)
Budget Amount *help	¥1,300,000 (Direct Cost: ¥1,300,000) Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Keywords	HCV / Immune response
Research Abstract	1.Activation of latent TGF-βcomplex by synthetic peptides Two synthetic peptides (Peptide A : KRFKQDGGWSHWSPWSS ; Peptide B : KRFK) were revealed to have low potentiality of latent TGF-43 complex activation. It was elucidated that the two peptides could not be available for enzyme linked immunospot (ELISpot) assay of TGF-β. 2.Constitutive TGF-β production in PBMC Major component of constitutive TGF-β production in peripheral blood mononuclear cells (PBMC) which was non-specific for HCV was revealed to be monocyte fraction. 3.Inhibition of TGF-βproduction in PBMC by HCV protein PBMC were prepared from 13 chronic hepatitis C patients (CH(C)) and 4 healthy people. After 4 hour-incubation of PBMC in the medium with or without HCV core protein or NS3 protein, the PBMC were cultured for additional 16 hours without HCV protein, then the concentration of TGF-βin the supernatant of the cultured medium was estimated by enzyme immunoassay (EJA). The concentration of TGF-βin the cultured medium of PBMC from CH(C) patients was reduced by 59.2+7.0% by the existence of HCV core protein in the medium and that of PBMC from healthy people was reduced by 73.2+16.5%. The production of TOF.43 of PBMC from CH(C) patients was reduced by 53.7±8.3% by HCV NS3 protein) although that from healthy people was not significantly reduced by NS3 protein. The core and NS3 proteins of HCV reduce TGF-βproduction and secretion by PBMC. The mechanism remains to be unknown. It may play some role in the pathogenesis of HCV-induced chronic hepatitis.