Polyfunctional Cytomegalovirus-Specific CD4+and pp65 CD8+T Cells Protect Against High-Level Replication After Liver Transplantation

Polyfunctional Cytomegalovirus-Specific CD4+and pp65 CD8+T Cells Protect Against High-Level Replication After Liver Transplantation
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DOI:
10.1111/j.1600-6143.2008.02425.x
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发表时间:
2008-12-01
影响因子:
8.8
通讯作者:
Emery, V. C.
Emery, V. C.
中科院分区:
医学2区
文献类型:
--
作者:
Nebbia, G.;Mattes, F. M.;Emery, V. C.

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被引文献

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为了确定针对人巨细胞病毒(HCMV)的多功能CD 4 + T细胞应答结合CD 8 + T细胞应答是否是控制HCMV复制的关键,我们前瞻性地分析了29名肝移植受者针对可溶性HCMV抗原、pp 65和IE 1蛋白的CD 4 + T细胞应答,CD 8 + T细胞对pp 65和IE 1蛋白以及一系列辅助性T细胞(Th)1和Th 2细胞因子的应答。11例患者(38%)在肝移植后中位数21天(范围17-31天)发生HCMV DNA血症。在DNA血症患者中,产生IFN γ、IFN γ + IL 2和IL 2的总HCMV CD 4 + T细胞和产生IFN γ的pp 65-CD 8 + T细胞的频率和绝对数量显著降低。Th 1和Th 2细胞因子的数量在移植后的第一个20天内存在并不能预测DNA血症。在移植后的前20天内,0.1%裂解物刺激的产生IL 2的CD 4 + T细胞和产生IFN γ的pp 65-CD 8 + T细胞的临界水平高于0.4%,DNA血症的阳性和阴性预测值分别为54%和100%以及50%和92%。移植后早期测量多功能CD 4 + T细胞抗HCMV的能力可能有助于进行有针对性的干预,以最大限度地减少HCMV复制的发生以及急性和长期后果。
To determine whether polyfunctional CD4+ T-cell responses coupled with CD8+ T-cell responses against human cytomegalovirus (HCMV) are key to the control of HCMV replication we prospectively analyzed 29 liver transplant recipients for CD4+ T-cell responses against soluble HCMV antigen, pp65 and IE1 proteins, CD8+ T-cell responses against pp65 and IE1 proteins and a range of T helper (Th) 1 and Th2 cytokines. Eleven patients (38%) developed HCMV DNAemia at a median of 21 days post-liver transplantation (range 17-31 days). There was a significantly lower frequency and absolute number of total HCMV CD4+ T cells producing IFN gamma, IFN gamma+IL2 and IL2 and pp65-CD8+ T cells producing IFN gamma in patients with DNAemia. The quantities of Th1 and Th2 cytokines present during the first 20 days posttransplant were not predictive of DNAemia. Cut-off levels during the first 20 days posttransplant of 0.1% of lysate stimulated CD4+ T cells producing IL2, and pp65-CD8+ T cells producing IFN gamma above 0.4% had positive and negative predictive values for DNAemia of 54% and 100% and 50% and 92%, respectively. Measuring polyfunctional CD4+ T cells against HCMV early posttransplant may allow targeted intervention to minimize the occurrence and acute and long-term consequences of HCMV replication.