Circulating alloreactive T cells correlate with graft function in longstanding renal transplant recipients
Circulating alloreactive T cells correlate with graft function in longstanding renal transplant recipients
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DOI：
10.1681/asn.2007050539
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发表时间：
2008-07-01
影响因子：
13.6
通讯作者：
Reinke, Petra
中科院分区：
文献类型：
--
作者：
Bestard, Oriol;Nickel, Peter;Reinke, Petra
器官移植后监测同种异体反应性T细胞可使免疫抑制个体化。T细胞同种异体识别有两条途径与慢性移植物功能障碍有关：直接途径(受体T细胞对供体抗原提呈细胞提呈的供体多肽产生反应)和间接途径(供体多肽由受体抗原提呈细胞处理和提呈)。以前的研究只在肾移植后的头两年评估了这些同种反应，所以这项研究使用高灵敏度的干扰素-伽马ELISPOT试验，将34例长期存活的肾移植受者的循环中供者反应性记忆/效应性T细胞的存在与这两种途径相关联。值得注意的是，59%的患者直接激发了供者反应性T细胞，它们的存在与血清肌酐直接相关(P=0.001)，与估计的肾小球滤过率呈负相关(P=0.042)。多变量分析显示，直接的供者特异性T细胞的低反应性是唯一与移植物功能显著相关的变量，而抗供者间接同种异体反应性是唯一与蛋白尿显著相关的变量。有趣的是，当两条同种异体识别途径一起考虑时，无法检测到的直接同种异体反应性的患者有更好的长期移植物功能，不依赖于间接途径的同种异体致敏作用。总之，由两种途径启动的循环供体特异性同种异体反应性T细胞在移植后很长一段时间内仍可被检测到，并与移植物损伤有关。对同种异体反应性记忆/效应T细胞的评估可能有助于将来为移植受者量身定制个体化的免疫抑制方案。
Monitoring for alloreactive memory T cells after organ transplantation may allow individualization of immunosuppression. Two pathways of T cell allorecognition have been implicated in chronic graft dysfunction: Direct (recipient T cells respond to donor peptides presented by donor antigen-presenting cells) and indirect (donor peptides are processed and presented by recipient antigen-presenting cells). Previous studies have assessed these alloresponses only during the first 2 yr after kidney transplantation, so this study correlated the presence of circulating donor-reactive memory/effector T cells, primed by both pathways, in 34 longstanding living-donor renal transplant recipients using the highly sensitive IFN-gamma Elispot assay. Remarkably, 59% of patients had directly primed donor-reactive T cells, and their presence correlated directly with serum creatinine (P = 0.001) and inversely with estimated GFR (P = 0.042). Multivariate analysis revealed that hyporesponsiveness of direct, donor-specific T cells was the only variable that significantly correlated with graft function and that antidonor indirect alloreactivity was the only variable that significantly correlated with proteinuria. Interestingly, when both allorecognition pathways were considered together, patients with undetectable direct alloreactivity had better longterm graft function, independent of allosensitization by the indirect pathway. In conclusion, circulating donor-specific alloreactive T cells primed by both pathways are detectable long after transplantation and are associated with graft injury. Assessment of alloreactive memory/effector T cells might be helpful to tailor individual immunosuppression regimens for transplant recipients in the future.