Innate immune signals in allogeneic hematopoietic stem cell transplantation

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860775
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Hokkaido University
• Principal Investigator: SHIRATORI Souichi 北海道大学, 医学(系)研究科(研究院), 客員研究員 (00645905)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 造血幹細胞移植 / 移植片対宿主病 / GVHD / 移植片対白血病効果 / Toll Like Receptor / MyD88 / 白血病 / T細胞

Outline of Final Research Achievements

Among several innate immune signaling molecules, MyD88 in donor T cells were critical for the maximization of graft versus host disease (GVHD) after murine allogeneic bone marrow transplantation. T cells lack of single upstream molecules of MyD88 caused equivalent GVHD compared to wild type T cells, indicating that an overall blockade of MyD88-dependent signals in T cells are required for GVHD amelioration. MyD88 deficient T cells showed severely impaired Th1 response compared to wild type T cells upon CD3/CD28 stimulation and allogeneic stimulation. MyD88 deficient donor T cells exerted significant graft versus leukemia effects, suggesting that MyD88 inhibitor is a promising therapeutic reagent against GVHD in clinical transplantation.

Free Research Field

造血幹細胞移植