Exploration of organ specific antigen regulated by regulatory T cells in a mechanism of transplant tolerance

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16268
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: St. Marianna University School of Medicine (2021); Toho University (2018-2020)
• Principal Investigator: Shinoda Kazunobu 聖マリアンナ医科大学, 医学部, 教授 (60348737)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 制御性T細胞 / 臓器移植 / 免疫寛容

Outline of Final Research Achievements

We created mixed chimeras between C57BL/6-Foxp3-DTR recipients and F1 donors (C57BL/6-FoxpeDTR x 61620; DBA/2). Both recipient and donor-derived lymphocytes coexisted and chimeras had donor-specific tolerance against transplanted organs (skin or heart). Organ transplant tolerance was broken if regulatory T cells were depleted. We also created C57BL/6-Rag1 KO recipients, lacking both T and B cells, that received both skin and heart from DBA/2 donors, and adoptively transferred splenocytes from mixed chimeras that rejected skin or heart of DBA/2. In Rag1 KO recipients, the organs (skin or heart) that were rejected in mixed chimeras were rejected again after adoptive transfer of splenocytes, although allograft tolerance against the other organ (skin or heart) that were not rejected by mixed chimeras persisted after adoptive transfer. These results suggested that organ allograft tolerance in mixed chimeras was established against organ specific antigens regulated by regulatory T cells.

Free Research Field

移植免疫

Academic Significance and Societal Importance of the Research Achievements

混合キメラにおけるドナー特異的免疫寛容は、末梢における制御性T細胞を消去すると破綻することがわかったが、そのメカニズムとして制御性T細胞が臓器特異的抗原を対象として免疫寛容を成立させていることが示唆された。