| Project/Area Number |
63570592
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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 | THE INSTITUTE OF MEDICAL SCIENCE, UNIVERSITY OF TOKYO |
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Principal Investigator |
AKIYAMA Nobuo The Institute of Medical Science, University of Tokyo, Organ Transplantation, Professor, 医科学研究所, 教授 (80012748)
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| Co-Investigator(Kenkyū-buntansha) |
WAKABAYASHI Tomo The Institute of Medical Science, University of Tokyo, Pathology, Assistant Prof, 医科学研究所, 講師 (90092379)
BECK Yoshifumi The Institute of Medical Science, University of Tokyo, Organ Transplantation, As, 医科学研究所, 助手 (70199454)
MITA Kunji The Institute of Medical Science, University of Tokyo, Organ Transplantation, As, 医科学研究所, 助手 (30190672)
NAGAO Takeshi The Institute of Medical Science, University of Tokyo, Organ Transplantation, As, 医科学研究所, 助教授 (90143487)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Organ Transplantation / Mechanism of Graft Acceptance / Major Histocompatibility Complex Antigens / Immunosuppression / 生着メカニズム |
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| Research Abstract |
The mechanisms of long-term graft tolerance have been studied by focusing mainly on immunological changes in allograft recipients, but never on expression of major histocompatibility complex (MHC) antigens in the grafts. In the present study, we looked at the MHC expression in rats, and human renal transplant biopsies in an attempt to relate the reduced MHC expression of the grafts to the graft acceptance by recipients.
In an experimental study using rats, MHC expression on tissues of kidney and heart were compared between normal animals and cyclosporine (CYA)-treated ones. Treatment with CYA resulted in little change in the MHC expression on these tissues. Hearts of CYA-treated rats, however, showed diminished expression of class I antigens and class II antigens recognizable by polymorphic monoclonal antibodies (MoAb) on the vascular endotherial cells.
In the analysis of human renal transplant biopsies, more than 80% of sections expressing HLA-DR or DP antigens on tubular cells were obtained at the time of acute rejection crisis. Furthermore, all sections expressing HLA-DQ antigens were obtained from the recipients having an acute rejection episode.
The expression of HLA-DR antigens on tubular cells was strongly enhanced in recipients who had had multiple pretransplant blood transfusions. Half of six biopsies on renal allografts functioning well longer than three years expressed HLA-DR and DP antigens on tubular cells. Donor-specific blood transfusions (DST) prior to transplantation might account for such intensified class II expression.
Our anticipation that diminishing of the FIHC expression of the grafts might be involved in the mechanisms by which recipients become tolerant of allograft could not be fully proved in this study. The present study only pointed out that MHC expression on tubular cells was enhanced while acute rejection crisis and that blood transfusions possibly affected the MHC expression there as well.
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