Elucidation of function and clinical significance of human acute GVHD tissue-infiltrating T cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Shiga University of Medical Science (2022-2023); Nagoya University (2021)
• Principal Investigator: Murata Makoto 滋賀医科大学, 医学部, 教授 (40378063)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 造血幹細胞移植 / 移植片対宿主病 / T細胞

Outline of Final Research Achievements

To analyze the characteristics of immune cells in the acute GVHD tissues, we obtained GVHD biopsy tissues from patients who developed acute GVHD with written informed consent. Five T-cell clones were successfully isolated from a skin biopsy tissue of a patient with skin acute GVHD. STR-PCR analysis demonstrated that four T-cell clones were derived from donor. However, a T-cell clone which accounted for 23% of skin tissue-infiltrating T cells was derived from the recipient. We obtained more than one biopsy tissues from patients who developed refractory acute GVHD. Almost all of dominant T-cell clones in the tissues before the first-line GVHD treatment decreased, and new T-cell clones expanded in the tissues after the first-line GVHD treatment. These data suggest that the residual recipient T cells may contribute to develop acute GVHD and that the emergence of new T-cell clones during the first-line GVHD treatment may contributes to the refractoriness of GVHD to the first-line treatment.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

得られた研究結果は、急性GVHDの発症にはドナーT細胞に加えてレシピエントT細胞も関与している可能性、そして急性GVHD一次治療開始時に組織に浸潤していたT細胞クローンとは異なる新たなT細胞クローンがGVHD組織に浸潤することによってそのGVHDは治療不応性となる可能性を示唆している。ヒトの移植後急性GVHD組織に浸潤するT細胞に焦点を当てた研究は極めて限られており、この研究成果はヒト急性GVHD発症メカニズムのさらなる解明に貢献すると考えられる。また、急性GVHDの新しい診断・予防・治療戦略の開発に資するものと期待される。