2009 Fiscal Year Final Research Report

Establishmentof a strategy to regulate alloreactive T cells by CD14^+monocyte-derived endothelial-like cells for applying in organ transplantation

Research Project

Project/Area Number	20790931
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	General surgery
Research Institution	Hiroshima University
Principal Investigator	TANAKA Yuka Hiroshima University, 大学院・医歯薬学総合研究科, 助教 (90432666)
Project Period (FY)	2008 – 2009
Keywords	臓器移植 / 免疫寛容 / 内皮細胞
Research Abstract	We have established a strategy to inhibit alloreactive T cells without nonspecific immunosuppressants by using immune-regulatory endothelial-like cells (ELCs) derived from peripheral blood CD14^+ monocytes. We have also attempted to establish an in vivo mouse model to investigate the strategy to regulate alloreactive T cells (i.e. liver endothelia-chimeric Rag-2/γ-chain double knockout mice reconstructed with syngeneic T cells). The ELCs regenerated from peripheral blood CD14+ monocytes expressed MHC class II, CD80 and CD86 together with PDL-1 and ILT-3 (inhibitory molecules against T cells). Adding the stimulator-type ELCs into the culture of mixed reaction assay resulted in the significant inhibition of T cell proliferation in the stimulator-specific fashion. These findings suggest that adoptive transfer with the ELCs regenerated from donor peripheral blood CD14^+ monocytes specifically induces tolerance among alloreactive T cells in organ transplantation.