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

我们已经建立了一种不使用非特异性免疫抑制剂，通过使用外周血CD 14 ^+单核细胞来源的免疫调节性内皮样细胞（ELC）来抑制同种异体反应性T细胞的策略。我们还尝试建立体内小鼠模型以研究调节同种异体反应性T细胞的策略（即用同基因T细胞重建的肝内皮嵌合Rag-2/γ-链双敲除小鼠）。从外周血CD 14+单核细胞再生的ELC表达MHC II类、CD 80和CD 86以及PDL-1和ILT-3（针对T细胞的抑制分子）。在混合反应培养物中加入刺激因子型ELC，可显著抑制T细胞的增殖，且具有刺激因子特异性。这些发现表明，过继转移供体外周血CD 14 ^+单核细胞再生的ELC可特异性诱导器官移植中同种异体反应性T细胞的耐受。

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.