Investigation of the mechanisms underlying humoral immunodeficiency following GVHD

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460491
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo
• Principal Investigator: Satoshi Ueha 東京大学, 医学(系)研究科(研究院), 講師 (00447385)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 移植免疫 / 造血幹細胞移植 / GVHD / 液性免疫 / リンパ節

Outline of Final Research Achievements

This study focused on the pathogenesis of prolonged humoral immunodeficiency following allogeneic hematopoietic stem cell transplantation (allo-HSCT). In a mouse allo-HCST model, mice with a history of CD8+ T cell-mediated GVHD developed severe atrophy of the lymph nodes and failed to mount T-cell dependent humoral immune responses to subcutaneous or oral immunization. Lymph node fibroblastic reticular cells were impaired in the early phase of GVHD through Fas-FasL dependent cytotoxicity, and inhibition of FasL partially ameliorated lymph node impairment. Depletion of CD8+ T cells in the graft or inhibition of FasL signaling would be expected to prevent lymph node GVHD and humoral immunodeficiency.

Free Research Field

医歯薬学