Treatment-dependent Loss of Polyfunctional CD8+T-cell Responses in HIV-infected Kidney Transplant Recipients Is Associated with Herpesvirus Reactivation
Treatment-dependent Loss of Polyfunctional CD8+T-cell Responses in HIV-infected Kidney Transplant Recipients Is Associated with Herpesvirus Reactivation
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DOI：
10.1111/j.1600-6143.2008.02539.x
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发表时间：
2009-04-01
影响因子：
8.8
通讯作者：
Brander, C.
中科院分区：
文献类型：
--
作者：
Gasser, O.;Bihl, F.;Brander, C.
抗逆转录病毒疗法极大地改变了艾滋病毒感染的进程，艾滋病毒感染者(艾滋病毒(+))越来越有资格接受实体器官移植。然而，关于免疫抑制(IS)策略如何与移植结果和免疫功能相关的数据很少。我们在27名HIV(+)肾移植受者的一年前瞻性队列中，确定了移植和免疫耗竭治疗对CD4+T细胞计数、HIV-、EBV-和巨细胞病毒(CMV)病毒载量以及病毒特异性T细胞免疫的影响。虽然结果显示，随着时间的推移，疱疹病毒特异性细胞毒性T细胞(CTL)反应的广度和幅度不断增加，但他们也显示，在接受胸腺球蛋白作为淋巴细胞耗尽治疗的个体中，多功能病毒特异性CTL显著耗尽。多功能CTL的消失伴随着病毒学的EBV再激活事件，直接将特异性多功能CTL的缺失与病毒的再激活联系在一起。这些数据首次提供了对感染HIV+的移植受者的免疫储备的洞察，并突出了胸腺球蛋白治疗的新的免疫学效果。需要进行长期研究来评估胸腺球蛋白治疗相关的临床风险，特别是EBV相关淋巴增生性疾病。
Antiretroviral-therapy has dramatically changed the course of HIV infection and HIV-infected (HIV(+)) individuals are becoming more frequently eligible for solid-organ transplantation. However, only scarce data are available on how immunosuppressive (IS) strategies relate to transplantation outcome and immune function. We determined the impact of transplantation and immune-depleting treatment on CD4+ T-cell counts, HIV-, EBV-, and Cytomegalovirus (CMV)-viral loads and virus-specific T-cell immunity in a 1-year prospective cohort of 27 HIV(+) kidney transplant recipients. While the results show an increasing breadth and magnitude of the herpesvirus-specific cytotoxic T-cell (CTL) response over-time, they also revealed a significant depletion of polyfunctional virus-specific CTL in individuals receiving thymoglobulin as a lymphocyte-depleting treatment. The disappearance of polyfunctional CTL was accompanied by virologic EBV-reactivation events, directly linking the absence of specific polyfunctional CTL to viral reactivation. The data provide first insights into the immune-reserve in HIV+ infected transplant recipients and highlight new immunological effects of thymoglobulin treatment. Long-term studies will be needed to assess the clinical risk associated with thymoglobulin treatment, in particular with regards to EBV-associated lymphoproliferative diseases.