Grant-in-Aid for Scientific Research (A)
|Research Institution||KYOTO UNIVERSITY|
INOMATA Yukihiro Kyoto University, Dpt.of Transplantation Immunology, Associate Professor, 医学研究科, 助教授 (50193628)
SUZUKI Seiichi National Childrens, Medical Reserch Center, Dpt.of Experimental Surgery and Bio, 実験外科生体工学部, 部長 (00111386)
WAKATSUKI Yoshio Kyoto University, Dpt.of Geriatric Medicine, Lecturer, 医学研究科, 講師 (40220826)
ASONUMA Kastuhiro Kyoto University, Dpt.of Transplantation Immunology, Assistant, 医学研究科, 助手 (40202626)
UEMOTO Shinji Kyoto University, Dpt.of Transplantation Immunology, Assistant, 医学研究科, 助手 (40252449)
TANAKA Koichi Kyoto University, Dpt.of Transplantation Immunology, Professor, 医学研究科, 教授 (20115877)
|Project Fiscal Year
1997 – 1998
Completed(Fiscal Year 1998)
|Budget Amount *help
¥25,700,000 (Direct Cost : ¥25,700,000)
Fiscal Year 1998 : ¥7,900,000 (Direct Cost : ¥7,900,000)
Fiscal Year 1997 : ¥17,800,000 (Direct Cost : ¥17,800,000)
|Keywords||small bowel transplantation / pig / rejection / apoptosis / Tacrolimus / 小腸移植 / ブタ / 拒絶反応 / アポトーシス / タクロリムス / TUNEL法 / 免疫抑制 / FTY720|
Background : The experience with clinical living donor SBT(small bowel transplantation) motivate us to research on the following problems, which have been the obstacles to the improvement of graft and/or patient survival.
Earlier and definite diagnosis of rejection
More sophisticated way to control rejection
Pig SBT model : Pigs are adopted for our experiment because of the anatomical, physiological and immunological similarity between humans and pigs. We established one-staged orthotopic SBT model using donors and recipients which showed alloreactivity with mixed lymphocyte reaction.
Sampling of specimens :
a) drug administration and blood sampling through central line
b) fiberscopy (using clinical pediatric fiber) and biopsy
We established techniques above with pig SBT model and are performing these safely and regularly, which enable us to monitor the rejection process at the same level for clinical transplantation.
Results : Based on the macroscopic and microscopic findings, severity of rej
ection and its relationship to ABC (apoptotic body counts) were analyzed under the immunosuppression with Tacrolimus, which has been the key drug for clinical SBT.Samples from grafts with rejection presented higher ABC (6.59/l0crypts) than those from non-rejected grafts (ABC ; 0.773/l0crypts), which showed statistical difference. There was no correlation between the severity of rejection and ABC.
Immunohistochemical studies were performed to analyze the induction pathway to apoptosis. Infiltration of CD8+ lymphocytes and FasL+ lymphocytes around crypts and increased expression of TNF receptor on epithelial cells were observed at the same time with, or prior to, macroscopic and/or histological rejection.
Future prospects and plans : The rejection in pig SBT now can be analyzed more in detail with the indicators above. Using the indicators, we are moving on to the further research projects such as local administration of immunosuppressants or tolerance induction. These indicators will be applied for our coming clinical SBT cases for the diagnosis of rejection. Less