William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, Minnesota, USA.
Human Cellular Therapy Laboratory, Mayo Clinic, Rochester, Minnesota, USA.
Kidney Int. 2018 Jun;93(6):1465-1474. doi: 10.1016/j.kint.2018.01.022. Epub 2018 Apr 12.
Kidney allografts of patients who undergo simultaneous liver-kidney transplantation incur less immune-mediated injury, and retain better function compared to other kidney allografts. To characterize the host alloimmune responses in 28 of these patients, we measured the donor-specific alloresponsiveness and phenotypes of peripheral blood cells after the first year. These values were then compared to those of 61 similarly immunosuppressed recipients of a solitary kidney or 31 recipients of liver allografts. Four multicolor, non-overlapping flow cytometry protocols were used to assess the immunophenotypes. Mixed cell cultures with donor or third party cells were used to measure cell proliferation and interferon gamma production. Despite a significant overlap, simultaneous liver-kidney transplant recipients had a lower overall frequency of circulating CD8, activated CD4 and effector memory T cells, compared to solitary kidney transplant recipients. Simultaneous liver-kidney transplant recipient T cells had a significantly lower proliferative response to the donor cells compared to solitary kidney recipients (11.9 vs. 42.9%), although their response to third party cells was unaltered. The frequency of interferon gamma producing alloreactive T cells in simultaneous liver-kidney transplant recipients was significantly lower than that of solitary kidney transplant recipients. Flow cytometric analysis of the mixed cultures demonstrated that both alloreactive CD4 and CD8 compartments of the simultaneous liver-kidney transplant recipient circulating blood cells were smaller. Thus, the phenotypic and functional characteristics of the circulating blood cells of the simultaneous liver-kidney transplant recipients resembled those of solitary liver transplant recipients, and appear to be associated with donor-specific hypo-alloresponsiveness.
在同时进行肝肾移植的患者中，移植的肾异体移植物所受到的免疫介导损伤较小，且功能保留优于其他肾异体移植物。为了描述 28 例此类患者的宿主同种异体免疫反应，我们在第 1 年后测量了外周血单个核细胞的供体特异性同种反应性和表型。然后将这些值与 61 例单独接受肾移植或 31 例接受肝移植的患者的相应值进行比较。使用四个多色、非重叠的流式细胞术方案来评估免疫表型。使用供体或第三方细胞的混合细胞培养来测量细胞增殖和干扰素γ产生。尽管存在显著重叠，但与单独接受肾移植的患者相比，同时进行肝肾移植的患者循环中的 CD8、活化的 CD4 和效应记忆 T 细胞的总体频率较低。与单独接受肾移植的患者相比，同时进行肝肾移植的患者 T 细胞对供体细胞的增殖反应显著降低（11.9%对 42.9%），尽管对第三方细胞的反应没有改变。同时进行肝肾移植的患者产生干扰素γ的同种反应性 T 细胞的频率明显低于单独接受肾移植的患者。混合培养的流式细胞术分析表明，同时进行肝肾移植患者循环血液中的同种反应性 CD4 和 CD8 细胞群均较小。因此，同时进行肝肾移植患者循环血液细胞的表型和功能特征类似于单独进行肝移植的患者，并且似乎与供体特异性低同种反应性有关。
