1998 Fiscal Year Final Research Report Summary
Anti-allo immune response in the liver after inoculation of allogeneic antigen
| Project/Area Number |
09671230
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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 |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
DONO Keizo Osaka University Medical School, Assistant Professor, 医学部, 助手 (60283769)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Keywords | immunological tolerance / rat liver transplantation / rat heart transplantation / donor antigen inoculation / liver |
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| 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
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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
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[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
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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