| Project/Area Number |
10670517
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | AICHI MEDICAL UNIVERSITY |
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Principal Investigator |
TETSUYA Ishikawa AICHI MEDICAL UNIVERSITY,FIRST DEPARTMENT OF INTERNAL MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (10288508)
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| Co-Investigator(Kenkyū-buntansha) |
KAKUMU Hinichi AICHI MEDICAL UNIVERSITY,FIRST DEPARTMENT OF INTERNAL MEDICINE, PROFESSOR, 医学部, 教授 (10115545)
SUGIYAMA Hirotaka AICHI MEDICAL UNIVERSITY,FIRST DEPARTMENT OF INTERNAL MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (70242112)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | HEPATITIS B VIRUS / TRANSGENIC MOUSE / CYTOTOXIC T LYTMPHOCYTE / ANTI-VIRAL EFFECT / ANTI-INFLAMMATORY THERAPY / MUTATED PEPTIDE / ANTOGONIST / VACCINE / 慢性肝炎 / costimulatory molecule / TCR / サイトカイン / ケモカイン / DNA immunization |
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| Research Abstract |
Hepatitis B virus (HBV) transgenic mouse(Tg) was used to analyze immunopathogenesis of viral hepatitis. Hepatic injury in HBV-Tg after adoptive transfer of HBsAg-specific cytotoxic T lymphocytes (CTL) was monitored. Simultaneously anti-viral effect of CTL was assessed by measuring HBV mRNA remaining in the liver of Tg 5 days after CTL transfer. Using CTLs with same specificity but with different cytokine profiles, the effects of individual CTLs on disease severity and viral elimination were analyzed. Anti-viral effect of CTLs well-correlated with the amount of cytokines produced by CTLs, such as IFN-ィイD2γィエD2, however the extent of hepatic injury die not correlated with the amount of those cytokines. These results suggest that the severity of hepatitis is affected by the characteristics of CTLs other than their cytokine profiles. The more detailed study is needed to apply these observations to the anti-inflammatory therapy or hepatitis that does not disturb the clearance of the virus
HBsAg-specific CTL clones in H-2d mouse recognize the peptide that located the residue 28-39 of HBsAg. In spite of the different T cell receptor (TCR)βgene usage, they all recognize the risidue 33 as TCR contact site. We made 19 mutated peptides with all the possible substitutions at residues 33 to find antagonist peptides that can reduce the severity of hepatitis by in vivo administration. The analysis is now in progress. Among the mutated peptides of HBsAg 28-39, we found several peptides with higher affinity to MHC molecule than wild type peptide, Furthermore some of these peptides were recognized more efficiently by CTL clone than wild type was. They may be the candidates for effective peptide vaccines to induce CTLs for the clearance of the virus.
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