1989 Fiscal Year Final Research Report Summary
Analysis of the mechanism of long-term acceptance of rat liver allografts and its application to organ transplantation
| Project/Area Number |
62570567
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Osaka University Medical School |
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Principal Investigator |
MONDEN Morito Osaka Univ. Med. Sch. Medical school lecturer, 医学部, 講師 (00127309)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Yoshiaki Osaka Univ. Hospital Surgical staff, 医学部付属病院, 医員
KANAI Toshio Osaka Univ. Med. Sch. Medical school assistant, 医学部, 助手 (50205051)
GOTOH Mitukazu Osaka Univ. Med. Sch. Medical school assistant, 医学部, 助手 (50162160)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Rat / Orthotopic liver transplantation / Immunological tolerance / Blocking factor / Antigen presentation / Oral tolerance / DTH (delayed type hypersensitivity) response / Antibody formation |
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| Research Abstract |
The relative resistance of liver grafts to rejection when compared with other organs, is well known. It would be useful for specific immunosuppression of other organ grafts to analyze the mechanisms involved in such phenomenon. In these experiments we revealed that liver allografts from ACI to Wistar rats permanently survived without immunosuppression and showed the existence of some serum factors from 2 to 4 weeks after liver grafting that prolong survival of heart allografts from same donor. Evidence for suppressor cell activity was not found. Then we analyzed the activity of blocking factors in in-vitro systems. however constant results were not obtained. We conclude that the mechanisms that. Induce long- term acceptance of liver allografts in this combination were multifactorial.
On the other hand, we found that liver allografts from ACI to BUF rats survived indefinitely when grafted 10 days after intraportal administration of ACI spleen cells. Thereafter we analyzed the immunologic
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al mechanisms for this phenomenon. We tested the effect of intraportal injection of donor spleen cells on antibody formation and DTH response. High titer of cytotoxic antibodies 1:64-1:256 were detected in intravenously-injected rats 7-10 days after injection, but not in intraportally-injected rats. Moreover intraportal injection abrogated antibody formation by subsequent intravenous one. DTH response was also suppressed by intraportal injection of ACI spleen cells. To investigate the immunological state of liver allograft-bearing rats, we transplanted simultaneously ACI and F344 rat skins to liver recipients surviving over 60 days. The animals did not reject ACI skin but rejected F344 rat skin in normal fashion.
In conclusion, this study revealed that intraportal injection of donor spleen cells causes active suppression of both DTH response and antibody formation, which results in long-term acceptance of liver allografts and induction of donor specific tolerance in the recipient rats. intraportal injection of donor spleen cells might be a promising modality for induction of specific tolerance in clinical liver transplantation. Less
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