In organ transplantation, a reproducible and robust immune-monitoring assay has not been established to determine individually tailored immunosuppressants (IS). We applied humanized mice reconstituted with human (hu-) peripheral blood mononuclear cells (PBMCs) obtained from living donor liver transplant recipients to evaluate their immune status. Engraftment of 2.5 × 10⁶ hu-PBMCs from healthy volunteers and recipients in the NSG mice was achieved successfully. The reconstituted lymphocytes consisted mainly of hu-CD3⁺ lymphocytes with predominant CD45RA⁻CD62L^lo T_EM and CCR6⁻CXCR3⁺CD4⁺ Th1 cells in hu-PBMC-NSG mice. Interestingly, T cell allo-reactivity of hu-PBMC-NSG mice was amplified significantly compared with that of freshly isolated PBMCs (p < 0.05). Furthermore, magnified hu-T cell responses to donor antigens (Ag) were observed in 2/10 immunosuppressed recipients with multiple acute rejection (AR) experiences, suggesting that the immunological assay in hu-PBMC-NSG mice revealed hidden risks of allograft rejection by IS. Furthermore, donor Ag-specific hyporesponsiveness was maintained in recipients who had been completely weaned off IS (n = 4), despite homeostatic proliferation of hu-T cells in the hu-PBMC-NSG mice. The immunological assay in humanized mice provides a new tool to assess recipient immunity in the absence of IS and explore the underlying mechanisms to maintaining operational tolerance.

在器官移植中，尚未建立可重复且强大的免疫监测测定法来确定单独定制的免疫抑制剂（IS）。我们应用从活着的供体肝移植受者获得的人（hu-）外周血单核细胞（PBMC）重构的人源化小鼠，以评估其免疫状态。成功地将2.5×10 ⁶ hu-PBMCs植入了健康志愿者和受体的NSG小鼠中。重组淋巴细胞主要由hu-CD3 ⁺淋巴细胞组成，其中CD45RA ^- CD62L ^lo T _EM和CCR6 ^- CXCR3 ⁺ CD4 ⁺hu-PBMC-NSG小鼠中的Th1细胞。有趣的是，与新鲜分离的PBMC相比，hu-PBMC-NSG小鼠的T细胞同种反应显着增强了（p <0.05）。此外，在具有多次急性排斥（AR）经历的2/10受免疫抑制的受体中观察到了对供体抗原（Ag）的hu-T细胞放大反应，这表明hu-PBMC-NSG小鼠的免疫学分析显示了同种异体移植被排斥的隐患是。此外，尽管hu-PBMC-NSG小鼠中hu-T细胞具有稳态增殖能力，但在完全脱离IS（n = 4）的受体中仍保持了供体Ag特异性低反应性。人源化小鼠的免疫学测定提供了一种新的工具，可用于评估缺乏IS时的受体免疫力，并探索维持操作耐受性的潜在机制。