Systemic varicella zoster virus reactive effector memory T-cells impaired in the elderly and in kidney transplant recipients
Systemic varicella zoster virus reactive effector memory T-cells impaired in the elderly and in kidney transplant recipients
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DOI：
10.1002/jmv.23427
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发表时间：
2012-12-01
影响因子：
12.7
通讯作者：
Weimar, Willem
中科院分区：
文献类型：
--
作者：
van Besouw, Nicole M.;Verjans, Georges M. G. M.;Weimar, Willem
水痘带状疱疹病毒（VZV）感染引起水痘，随后再激活带状疱疹。免疫功能低下的个体和老年人由于vzv特异性t细胞免疫功能减弱，患带状疱疹的风险很高。在本研究中，研究人员开发了一种新的功能性t细胞检测方法，以检测健康个体外周血中年龄与vzv特异性t细胞反应之间的相关性。其次，将肾移植受者的vzv特异性t细胞反应与健康个体进行比较。单核细胞分化为成熟的单核细胞来源的树突状细胞（moDCs），并感染VZV。t细胞与感染VZV的自体moDCs共培养，流式细胞术分析鉴定表型（即幼稚型[NA: CCR7+CD45RO-]，中央型[CM: CCR7+CD45RO+]和效应记忆型[EM: CCR7-CD45RO+] t细胞），并通过细胞内IFN-？flowcytometry。与NA和CM t细胞相比，vzv反应性CD4和CD8 EM t细胞的频率与年龄呈负相关（P = 0.0007和P = 0.01）。移植受者和对照组的vzv反应性CD4 NA、CM和EM t细胞百分比无差异。然而，与对照组相比，移植受者的vzv反应性CD8 EM t细胞的百分比显著降低（P = 0.02）。综上所述，感染VZV的moDCs是有效的抗原提呈细胞，适用于枚举和表征系统VZV特异性t细胞反应的表型和分化状态。数据表明，vzv反应性EM t细胞在老年人和肾移植受者中受损。中华医学杂志。84:2018205,2012。(c) 2012 Wiley期刊有限公司
Varicella zoster virus (VZV) infections cause varicella and subsequently herpes zoster upon reactivation. Immune-compromised individuals and the elderly are at high risk of developing herpes zoster due to waning of VZV-specific T-cell immunity. In the present study, a novel functional T-cell assay was developed to test the correlation between age and VZV-specific T-cell responses in peripheral blood from healthy individuals. Secondly, VZV-specific T-cell responses from renal transplant recipients were compared with healthy individuals. Monocytes were differentiated into mature monocyte-derived dendritic cells (moDCs) and were infected with VZV. T-cells were co-cultured with autologous moDCs infected with VZV and subjected to flowcytometric analysis to identify the phenotype (i.e., naive [NA: CCR7+CD45RO-], central [CM: CCR7+CD45RO+] and effector memory [EM: CCR7-CD45RO+] T-cells) and the frequency of VZV-reactive T-cell subsets by intra-cellular IFN-? flowcytometry. In contrast to NA and CM T-cells, the frequency of VZV-reactive CD4 and CD8 EM T-cells was inversely correlated with age (P?=?0.0007 and P?=?0.01). No difference was found in the percentage of VZV-reactive CD4 NA, CM and EM T-cells between transplant recipients and controls. However, the percentage of VZV-reactive CD8 EM T-cells was significantly lower in transplant recipients compared to controls (P?=?0.02). In conclusion, moDCs infected with VZV are efficient antigen presenting cells applicable to enumerate and characterize the phenotype and differentiation status of the systemic VZV-specific T-cell response ex-vivo. The data suggest that VZV-reactive EM T-cells are impaired in the elderly and renal transplant recipients. J. Med. Virol. 84:20182025, 2012. (c) 2012 Wiley Periodicals, Inc.