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Anti-allo immune response in the liver after inoculation of allogeneic antigen

Research Project

Project/Area Number 09671230
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionOsaka University

Principal Investigator

DONO Keizo  Osaka University Medical School, Assistant Professor, 医学部, 助手 (60283769)

Co-Investigator(Kenkyū-buntansha) NAGANO Hiroaki  Osaka University Medical School, Assistant Professor, 医学部, 助手 (10294050)
NAKAMORI Syoji  Osaka University Medical School, Assistant Professor, 医学部, 助手 (70294080)
UMESHITA Kouji  Osaka University Medical Hospital, Assistant Professor, 医学部・附属病院, 助手 (60252649)
SAKON Masato  Osaka University Medical School, Associate Professor, 医学部, 助教授 (40170659)
太田 博文  大阪大学, 医学・部附属病院, 医員
三好 秀幸  大阪大学, 医学部・附属病院, 医員
後藤 満一  大阪大学, 医学部, 助教授 (50162160)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsimmunological tolerance / rat liver transplantation / rat heart transplantation / donor antigen inoculation / liver / 肝網内系細胞
Research Abstract

There is a general agreement that a preferential accumulation of alloantigens within the liver could induce hyporesponsiveness to the inoculated antigens.Entrapment of antigens in the liver may evoke an unique immune response in the organ and play a key role in determination of the fate of the transplanted grafts.To understand the immune response in the liver after inoculation of allogeneic donor antigens, we examined the immune response to systemically inoculated alloantigen in rats whose sensitized liver was replaced with that of naive rats or in naive rats whose liver was replaced with that of sensitized rats.
Methods.Using implantation of syngeneic liver (alloantigen-accumulated/naive) in rats (naive/alloantigen sensitized), we compared the immune responses to alloantigen between rats with hepatic/extrahepatic alloantigen at 24 hours after alloantigen inoculation.This was called sensitized-liver-grafted (SLG)/ sensitized-liver-removed (SLR) treatment.The immune response to donor all … More oantigen in this model was evaluated by survival of skin or heart grafts, complement-dependent cytotoxicity (CDC) titer and delayed-type hypersensitivity (DTH) response.
Results.Compared with the mean survival time (MST) in donor spleen cell inoculated (DSI) rats (skin and heart, MST : 8.2*1.1 and 10.7*2.3 days), SLG rats rejected allografts in an accelerated fashion (skin and heart, MST : 5.5*0.5 and 4.2*0.8 days), associated with higher ODC titer and DTH response.In contrast, allograft survival was moderately prolonged in SLR (skin and heart, MST : 16.5*2.6 and 29.5*3.7 days) associated with suppressed CDC titer and DTH response.The survival of third-party allograft following SLG or SLR treatment (skin, MST : 9.3*1.5 or 9.7*0.6 days) indicated that immunological hyper/hyporesponsiveness was donor-specific.
Conclusions.A strong anti-donor immune response was induced by the transfer of donor antigen-baring liver to naive rats 24 hrs after alloantigen inoculation, while removal of the liver suppressed alloimmune response.Our results indicate that vigorous anti-alloimmune response occurred in the liver following systemic inoculation of donor spleen cells. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Li He: "Participation of the liver in generation of a vigorous anti-donor response following inoculation of donor spleen cells." Transplantation. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ota H.: "Microchimerism in thymus is associated with upregulated T helper type 1 cytokine transcription during cardiac allograft rejection in rats1,2." Transplantation. 67. 165-173 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y.: "Direct Antigen Presentation Through Binding of Donor Intercellular Adhesion Molecule-1 to Recipient Lymphocyte Function-Associated Antigen-1 Molecules in Xenograft Rejection." Transplantation. 65(8). 1094-1100 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda Y.: "Protection of islet allografts transplanted together with Fas ligand expressing testicellar allografts." Diabetologia. 41. 315-321 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Gotoh M: "Induction of Allograft Tolerance-An End to Immunosuppressive Therapy in Transplantation?" Bio Drugs. 8(1). 56-67 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] He L., Gotoh M., Dono K., Nagano H., Ota H., Ohta Y., Okuyama M., Takeda Y., Shimizu J., Grochowicki T., Sakon M., Monden M.: "Participation of the liver in generation of a vigorous anti-donor response following inoculation of donor spleen cells." Transplantation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ota H., Gotoh M., Ohzato H., He L., Tanigawa T., Nagano H., Dono K., Takeda Y., Okuyama M., Shimizu J., Umeshita K., Nakamori S., Sakon M., Nishisho I., Monden M.: "Microchimerism in thymus is associated with upregulated T helper type 1 cytokine transcription during cardiac allograft rejection in rats 1,2." Transplantation. 67. 165-173 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y., Gotoh M., Ohzato H., Fukuzaki T., Nishihara M., Dono K., Umeshita K., Sakon M., Yagita H., Okumura K., Tanaka T., Kawashima H., Miyasaka M., Monden M.: "Direct Antigen Presentation Through Binding of Donor Intercellular Adhesion Molecule-1 to Recipient Lymphocyte Function-Associated Antigen-1 Molecules in Xenograft Rejection." Transplantation. 65(8). 1094-1100 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda Y., Dono K., Nishihara M., Grochowicki T., Kimura F., Yoshida T., Ohta Y., Ota H., Ohzato H., Umeshita K., Takeda T., Matsuura N., Sakon M., Kayagaki N., Yagita H., Okumura Y., Miyasaka M., Monden M.: "Protection of islet allografts transplanted together with Fas ligand expressing testicellar allografts." Diabetologia. 41. 315-321 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Gotoh M,Miyasaka M., Ohzato H., Dono K., Umeshita K., Sakon M., Monden M.: "Induction of Allograft Tolerance - An End to Immunosuppressive Therapy in Transplantation?" Bio Drugs. 8(1). 56-67 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] LiHe: "Participation of the liver in generation of a vigorous anti-donor response following inoculation of donor spleen cells." Transplantation. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Ota H.: "Microchimerism in thymus is associated with upregulated T helper type1 cytokine transcription during cardiac allograft rejection in rats1,2" Transplantation. 67. 165-173 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimizu J.: "Evaluation of Regional Liver Function by Gadolinium-EOB-DTPA Enhanced MR imaging." Gastroenterology. 114. 1342 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohta Y.: "Direct Antigen Presentation Through Binding of Donor Intercellular Adhesion Molecule-1 to Recipient Lymphocyte Function-Associated Antigen-1 Molecuies in Xenograft Rejection." Transplantation. 65(8). 1094-1100 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyoshi H.: "Calpain-μ is activated in hepatocyte mitochondria during ischemia-reperfusion injury." Hepatology. 10. 255-259 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeda Y.: "Protection of islet allografts transplanted together with Fas ligand expressing testicellar allografts." Diabetologia. 41. 315-321 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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