1997 Fiscal Year Final Research Report Summary
Study of tolerance mechanism in a functional tolreance modrl of rat lung transplant
| Project/Area Number |
08457341
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
FUJIMURA Shigefumi Institute of Development, Aging and Cancer, Tohoku University.Professor, 加齢医学研究所, 教授 (40006078)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Yuji Institute of Development, Aging and Cancer, Tohoku University.Instructor, 加齢医学研究所, 助手 (80281997)
KONDO Takashi Institute of Developtment, Aging and Cancer, Tohoku University.Instructor, 加齢医学研究所, 助手 (10195901)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Lung Transplantation / Heart-Lung Transplantation / Pulmonary Preservation / Immunosuppression / Rejection Monitoring / Non-Heart-Beating Donor / 拒絶反応 |
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| Research Abstract |
Our previous studies have shown that a spontaneous functional tolerance develops in a rat model of lung transplantation. The tolerance observed in this model may be due to the minor histocompatible differences. To further examine this model, the effect of pre-transplant donor-specific spleen cell transfusions (DSTs) was examined on the functional tolerance state in this model.
F344 rats received WKY spleen cells on days-45 and-30 before transplantations. Control F344 rats received lung grafts without DSTs. Recipients in both groups were euthanized on day 7,14,21 and 49 post-transplant, and allograft rejection (AR) was graded stage 0-IV.Intragraft cytokine gene transcripts were examined using RT-PCR techniques. In addition, allogeneic and third party skin grafts were placed on recipients at day 35 to evaluate the development of systemic tolerance. Control animals showed stage II-III AR in the first 3 weeks followed by spontenous recovery with stage I-II AR on day 49. In contrast, DST animals showed stage Ill-IV AR by day14-21, without any evidence of recovery on day 49. WKY skin grafts showed prolonged survival in control animals, but were promptly rejected in DST animals. Intragraft cytokine gene expression in control animals was characterized by weak expression of IL-2 and high IL-10, while DST animals showed high levels of IL-2 transcripts.
Conclusions : 1) Pre-transplant DSTs did not enhance allograft survival, but induced AR and ablated tolerance in the WKY*F344 lung transplant model. 2) The DST-induced AR was associated with a deviation of cytokine immune responses from a predominant Th2 to Th1.3) Factors other than histocompatibility, such as route of alloantigen exposure, amount or nature of alloantigens associated specifically with lung allografts, are involved in deviating native immune responses toward acceptance in this model.
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