Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Am J Transplant. 2011 Jul;11(7):1388-96. doi: 10.1111/j.1600-6143.2011.03540.x. Epub 2011 May 12.
Induction therapy is used in kidney transplantation to inhibit the activation of donor-reactive T cells which are detrimental to transplant outcomes. The choice of induction therapy is decided based on perceived immunological risk rather than by direct measurement of donor T-cell reactivity. We hypothesized that immune cellular alloreactivity pretransplantation can be quantified and that blocking versus depleting therapies have differential effects on the level of donor and third-party cellular alloreactivity. We studied 31 kidney transplant recipients treated with either antithymocyte globulin (ATG) or an IL-2 receptor blocker. We tested pre- and posttransplant peripheral blood cells by flow cytometry to characterize T-cell populations and by IFN-γ ELISPOT assays to assess the level of cellular alloreactivity. CD8(+) T cells were more resistant to depletion by ATG than CD4(+) T cells. Posttransplantation, frequencies of donor-reactive T cells were markedly decreased in the ATG-treated group but not in the IL-2 receptor blocker group, whereas the frequencies of third-party alloreactivity remained nearly equivalent. In conclusion, when ATG is used, marked and prolonged donor hyporesponsiveness with minimal effects on nondonor responses is observed. In contrast, induction with the IL-2 receptor blocker is less effective at diminishing donor T-cell reactivity.
诱导治疗用于肾移植以抑制对移植结果有害的供体反应性 T 细胞的激活。诱导治疗的选择是基于感知的免疫风险，而不是通过对供体 T 细胞反应性的直接测量来决定的。我们假设移植前免疫细胞同种反应性可以被量化，并且阻断与耗竭治疗对供体和第三方细胞同种反应性的水平有不同的影响。我们研究了 31 名接受抗胸腺细胞球蛋白（ATG）或白细胞介素-2 受体阻滞剂治疗的肾移植受者。我们通过流式细胞术检测移植前后外周血细胞，以表征 T 细胞群体，并通过 IFN-γ ELISPOT 测定评估细胞同种反应性的水平。与 CD4(+) T 细胞相比，CD8(+) T 细胞对 ATG 的耗竭更具抵抗力。在 ATG 治疗组中，移植后供体反应性 T 细胞的频率明显降低，但在白细胞介素-2 受体阻滞剂组中则没有，而第三方同种反应性的频率几乎保持不变。总之，当使用 ATG 时，观察到明显且持久的供体低反应性，对非供体反应的影响最小。相比之下，用白细胞介素-2 受体阻滞剂诱导的效果在降低供体 T 细胞反应性方面效果较差。
