Immune escape and exhaustion attributing to development of PTLD

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17352
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Masaki Yamada 国立研究開発法人国立成育医療研究センター, 高度感染症診断部, 医長 (30445316)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: EBV / 小児 / 固形臓器移植 / 細胞疲弊

Outline of Final Research Achievements

EBV-associated lymphoproliferative disorders (LPD) are a group of disorders caused by the abnormal proliferation of EBV-infected cells. Among them, post-transplant lymphoproliferative disorder (PTLD) is thought to result from T-cell dysfunction due to the use of immunosuppressive agents. In this study, we attempted to create a PTLD model using humanized mice and elucidate the immune surveillance mechanisms related to T-cell exhaustion. However, in this model, EBV-specific T cells and replicate T-cell exhaustion were not appropriately reproduced, forcing a change in our approach. Consequently, we aimed to establish an experimental system using human peripheral blood mononuclear cells (PBMCs) to conduct single-cell RNA analysis and analyze the properties of EBV-infected cells.

Free Research Field

感染免疫学

Academic Significance and Societal Importance of the Research Achievements

小児移植患者における移植後リンパ増殖性疾患の病態およびそれと関連した危険因子の解明を目指した研究である。病態の解明やより優れた診断マーカーの発見に寄与しうる実験系の開発を行った。高度先進医療である移植治療を受けたのちに、合併症を制御し患者予後を改善するために重要な研究である。