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2018 Fiscal Year Final Research Report

Analysis of regulatory T cell function and gene expression for clinical implementation of transplantation tolerance induction

Research Project

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Project/Area Number 16K11071
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionTokyo Women's Medical University

Principal Investigator

TANABE Kazunari  東京女子医科大学, 医学部, 教授 (80188359)

Research Collaborator IKEMIYAGI masako  
ISHII yasuyuki  
ISHII rumi  
OKUMI masayoshi  
OMOTO kazuya  
KATSUMATA Haruki  
KAWAGUCHI emi  
KANZAWA taichi  
SAIGA kan  
HASEGAWA junpei  
HIRAI toshihito  
FUKUDA hironori  
MIYAIRI satoshi  
YAMAKAWA takafumi  
YOKOO takashi  
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords同種異系キメラ誘導 / 移植 / 免疫寛容 / タクロリムス / エベロリムス / 制御性T細胞
Outline of Final Research Achievements

We previously reported a mixed hematopoietic chimerism induction regimen that promotes regulatory T cell (Treg) proliferation by stimulating invariant natural killer T cells under CD40 blockade. Here we evaluated the impact of tacrolimus (TAC) or everolimus (EVL) on this regimen. In the immunosuppressive drug-dosing phase, peripheral blood chimerism was comparably maintained by both TAC and EVL. After dosing was discontinued, TAC-treated mice showed gradual graft rejection, whereas EVL-treated mice sustained long-term robust chimerism. Treg from TAC-treated mice showed lower expression of both Ki67 and cytotoxic T lymphocyte antigen-4, and lower suppressive activity in vitro than those from EVL-treated mice, indicating that TAC negatively impacted the regimen by interfering with Treg proliferation and activation. Our results suggest that the usage of calcineurin inhibitors should be avoided if utilizing the regimen to induce Treg for the establishment of mixed hematopoietic chimerism.

Free Research Field

泌尿器、腎移植、骨髄移植、免疫寛容

Academic Significance and Societal Importance of the Research Achievements

免疫寛容の確立は臓器移植患者における免疫抑制剤の永続的内服を不要とするだけでなく、自己免疫性疾患の根治治療にも応用可能である。しかし、臨床応用を考慮すると、移植後初期の拒絶反応を抑制するため従来の免疫抑制剤の一時的な併用は必須と考えられる。本研究では我々の報告した免疫寛容誘導モデルを用いて、免疫抑制剤が及ぼす影響を明らかとし、免疫寛容誘導における免疫抑制剤使用の在り方について意義深い提案ができたと考えられる。

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Published: 2020-03-30  

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