Project/Area Number |
07807059
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Keio University |
Principal Investigator |
HIBI Toshifumi (1996-1997) Keio University, School of Medicine, Professor, 医学部, 教授 (50129623)
渡辺 守 (1995) 慶應義塾大学, 医学部, 助手 (10175127)
|
Co-Investigator(Kenkyū-buntansha) |
WATANABE Mamoru Keio Cancer Center, Vice Director, Associate Professor, 診療部長(研究職)
AISO Sadakazu Keio University, School of Medicine, Professor, 医学部, 教授 (60138013)
ISHII Hiromasa Keio University, School of Medicine, Professor, 医学部, 教授 (20051500)
日比 紀文 慶応がんセンター, 助教授 (50129623)
|
Project Period (FY) |
1995 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
|
Keywords | AIDS / HIV / oral Immunization / IL-7 / mucosal immunology / transgenic mouse / cytotoxic Tlymphcyte / Cholera toxin / SIV |
Research Abstract |
This series of research was done to assess the therapeutic approach to AIDS by induction of virus-specific cytotoxic T lymphocytes (CTLs) in the intestinal mucosa. We have been trying to induce CTLs in the intestinal mucosa by oral immunization of HIV gag or env peptide conjugated with cholera toxin subunit B.Unfortunately, We have failed to induce CTLs against HIV infection by these approaches. We have found that intestinal epithelial cell-derived interleukin-7 (IL-7) mediated immune responses in the intestinal mucosa were impaired in the mucosa with AIDS enteropathy. IL-7 mRNA expression and protein production was down regulated in the AIDS intestinal mucosa. IL-7 has been shown to be crucial to induce and proliferate HIV gag specific CTLs. Moreover, we have demonstrated that IL-7 inhibits HIV infection in the intestinal epithelial cells. All these results indicate that abnormal IL-7-mediated immune regulation should be modified to induce AIDS virus-specific CTLs in the intestinal mucosa by oral immunization. Further studies are warranted to find the approaches to increase IL-7 expression in the intestinal mucosa.
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