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Induction of cytotoxic Tlymphocyters in the intestinal mucosa by oral immunization of SIV gag or env peptide conjugated with chorela toxin

Research Project

Project/Area Number 07807059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKeio 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)
KeywordsAIDS / 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.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Watanabe M, et al: "Interleukin-7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes" J Clin Invest. 95. 2945-2953 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kanai T, et al: "IL-15 stimulates the expansion of AIDS virus-specific CTL" J Immunol. 157. 3681-3687 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M, et al: "The serum factor from patients with ulcerative colitis that induces T cell proliferation in the mouse thymus in interleukin-7" J Clin Immunol. 17. 282-292 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M, et al: "Interleukin-7 transgenic mice develop chronic colitis with decrease of Interleukin-7 protein accumulation in the colonic mucosa" J Exp Med. 187. 389-402 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M, et al: "CD45RChighCD4^+ intestinal mucosal lymphocytes mediate chronic inflammation in the colonic mucosa of a novel rat colitis model induced by TNB immunization" Clin Immunol Immunopathol. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M, et al: "Administration of recombinant human IL-12 to chronically SICmacinfected rhesus monkeys" AIDS Res Hum Retroviruses. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M, et al: "Essentials of Mucosal Immunology" Intestinal epithelial cell-derived interleukin 7 as a regulatory factor for the intestinal mucosal lymphocytes, 597 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M, et al: "Excepta Medica" Dysregulation of mucosal IL-7ーmediated immune regulation in intestinalinflammation (in press), (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,et al.: "Interleukin-7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes." J Clin Invest. 95. 2945-2953 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kanai T,et al.: "IL-15 stimulates the expansion of AIDS verus-specific CTL." J Immunol. 157. 3681-3687 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,et al.: "The serum factor from patients with ulcerative colitis that induces T cell proliferation in the mouse thymus in interleukin-7." J Clin Immunol. 17. 282-292 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,et al.: "Interleukin-7 transgenic mice develop chronic colitis with decrease of interleukin-7 protein accumulation in the colonic mucosa." J Exp Med. 187. 389-402 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,et al.: "CD45RChighCD4^+ intestinal mucosal lymphocytes mediate chronic inflammation in the colonic mucosa of a novel rat colitis model induced by TNB immunization." Clin Immunol Immunopathol. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,et al.: "Administration of recombinant human IL-12 tochronically SICmac-infected rhesus monkeys" AID Res Hum Retroviruses. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,et al.: "Intestinal epithelial cell-derived interleukin 7 as a regulatory factor fot the intestinal mucosal lymphocytes." Essentials of Mucosal Immunology. (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,et al.: "Dysregulation of mucosal IL-7-mediated immune regulation in intestinal inflammation." Excepta Medica. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,et al: "The serumfactor frompatients with ulcerative colitis that induces T cell proliferation in the mouse thymus is interleukin-7." J Clin Immunol. 17. 282-292 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe M,et al.: "Interleukin-7 transgenic mice develop chronic colitis with decrease of interleukin-7 protein accumulation in the colonic mucosa." J Exp Med. 187. 389-402 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe,M et al.: "CD45RChighCD4^+ intestinal mucosal lymphocytes mediate chronic inflammation in the colonic mucosa of a novel rat colitis model induced by TNB immunization." Clin Immunol Immunopathol. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe M,et al.: "Administration of recombinant human IL-12 to chronically SIVmacinfected rhesus monkeys" AID Res Hum Retroviruses. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe M,et al.: "Excepta Medica" Dysregulation of mucosal IL-7-mediated immune regulation in intestinal inflammation (in press), (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kanai T,et al: "IL-15 stimulates the expansion of AIDS virus-specific CTL" J Immunol. 157. 3681-3687 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ezaki T.et al: "Deletion mapping on chromosome 1p in well-differentiated gastric cancer." Br J Cancer. 73. 424-428 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe M.et al: "Preferential activation of CD4+Vβ5.2/5.3+ intestinal intraepithelial lymphocytes in the inflamed lesions of Crohn's disease." Clin Immunol Immunopathol. 78. 130-139 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe M.et al: "The serum factor from patients with ulcerative colitis that induces T cell proliferation in the mouse thymus is interleukin-7." J Clin Immunol. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okamoto S,et al: "Synthetic analogue to the CDR3 region of VI domain in the CD4 molecule suppressed colonic inflammation with decrease of infiltrating CD45RBlow CD4+mucosal T cells" J Immunol. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ueno Y,et al: "Interleukin-7 transgenic mice develop chronic colitis with transgene expression and decrease of interleukin-7 protein expression in the colonic mucosa." J Exp Med. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe M,et al: "Academic Press" Intestinal epithelial cell-derived interleukin 7 as a regulatory factor for the intestinal mucosal lymphocytes. Essentials of Mucosal Immunology, 270-279 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe M, et al.: "Interleukin-7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes." J. Clin. Invest.95. 2945-2953 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watanabe M, et al.: "CD4+ intetinal lymphocytes in the pathogenesis of Crohn's disease." J. Gastroenterol.30. 73-75 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hibi T, et al.: "Immunosuppressive agents in the treatment of Crohn's disease and ulcerative colitis." J. Gastroenterol.30. 121-123 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watanabe M, et al.: "Preferential activation of CD4+Vβ5.2/5.3+intestinal intraepithelial lymphocytes in the inflamed lesions of Crohn's disease." Clin. Immunol. Immunopathol.78 (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 渡辺 守、他: "炎症性腸疾患における免疫異常-ヒト炎症性腸疾患における大腸上皮細胞由来インターロイキン7の役割" Medicina. 32. 515-520 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 渡辺 守、他: "炎症性腸疾患の新しい動物モデル" GI reserch. 3. 7-12 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watanabe M, et al.: "Essentials of Mucosal Immunology" Academic Press, Inc. (in press), (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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