Mitochondria regulates peripheral CD4 CD8 double negative T cells function

2024 Fiscal Year Final Research Report

• Project/Area Number: 23K19469
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Okayama University
• Principal Investigator: Seike Keisuke 岡山大学, 大学病院, 助教 (20976427)
• Project Period (FY): 2023-08-31 – 2025-03-31
• Keywords: DN-T cell / HSCT / GVHD

Outline of Final Research Achievements

First, we analyzed the dynamics of DN-T cells using a hematopoietic stem cell transplantation model mouse. We compared the number of DN-T cells in the spleen using a syngeneic model that does not cause GVHD and an allogeneic model that does cause GVHD. On day 7 after transplant, the percentage and absolute number of DN-T cells were significantly increased in the allogeneic group compared to the syngeneic group. This result suggests that DN-T cells are related to the pathology of acute GVHD. Next, we created T cells with electron transport complex II knocked out using a CRISPR-Cas9 lentiviral vector, however, the efficiency of knockout introduction was poor. We are currently creating SDHA KO mice.

Free Research Field

Immunology

Academic Significance and Societal Importance of the Research Achievements

DN T細胞は（1）少数ではあるが末梢血に存在、（2）抗腫瘍性、免疫抑制性、炎症誘発性など多くの機能を有する、（3）腫瘍選択的細胞障害効果、（4）GVHD抑制効果が判明している。DN-T細胞の機能制御機構を解明することにより、DN-T細胞の抗腫瘍効果を増強する方法に繋がり、造血幹細胞移植およびCAR-T細胞療法の有効性を向上させることができる。