The Avidity and Lytic Efficiency of the CTL Response to HTLV-1
The Avidity and Lytic Efficiency of the CTL Response to HTLV-1
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DOI：
10.4049/jimmunol.0900069
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发表时间：
2009-05-01
影响因子：
4.4
通讯作者：
Bangham, Charles R. M.
中科院分区：
文献类型：
--
作者：
Kattan, Tarek;MacNamara, Aidan;Bangham, Charles R. M.
在人类嗜T淋巴细胞病毒1型（HTLV-1）感染中，高频率的HTLV-1特异性CTL可与高前病毒载量稳定共存，并且前病毒载量与HTLV-1相关炎性疾病的风险密切相关。这些观察结果导致HTLV-1特异性CTL在控制HTLV-1复制中无效但有助于炎性疾病的发病机制的假设。但是来自宿主和病毒免疫遗传学和基因表达微阵列的证据表明，强CTL应答与低前病毒载量和低HAW/TSP风险相关。在这里，我们定量了HTLV-1特异性CD 8（+）细胞的频率，溶解活性和功能性亲和力在新鲜的，未经刺激的PBMC与自然HTLV-1感染的个人。CD 8（+）T细胞反应的裂解效率--每天每个CD 8（+）细胞清除的自体HTLV-1表达细胞的分数--与前病毒载量和自发前病毒表达率呈负相关。HTLV-1特异性CD 8（+）细胞的功能亲合力与其裂解效率密切相关。我们的结论是，有效的控制HTLV-1在体内依赖于CTL的裂解效率，这反过来又取决于抗原识别的CTL亲合力。CTL的质量决定了持续性HTLV-1感染中病毒-宿主平衡的位置。免疫学杂志，2009，182：5723-5729.
In human T-lymphotropic virus type 1 (HTLV-1) infection, a high frequency of HTLV-1-specific CTLs can co-exist stably with a high proviral load and the proviral load is strongly correlated with the risk of HTLV-1-associated inflammatory diseases. These observations led to the hypothesis that HTLV-1 specific CTLs are ineffective in controlling HTLV-1 replication but contribute to the pathogenesis of the inflammatory diseases. But evidence from host and viral immunogenetics and gene expression microarrays suggests that a strong CTL response is associated with a low proviral load and a low risk of HAW/TSP. Here, we quantified the frequency, lytic activity and functional avidity of HTLV-1-specific CD8(+) cells in fresh, unstimulated PBMCs from individuals with natural HTLV-1 infection. The lytic efficiency of the CD8(+) T cell response-the fraction of autologous HTLV-1-expressing cells eliminated per CD8(+) cell per day-was inversely correlated with both the proviral load and the rate of spontaneous proviral expression. The functional avidity of HTLV-1-specific CD8(+) cells was strongly correlated with their lytic efficiency. We conclude that efficient control of HTLV-1 in vivo depends on the CTL lytic efficiency, which depends in turn on CTL avidity of Ag recognition. CTL quality determines the position of virus-host equilibrium in persistent HTLV-1 infection. The Journal of Immunology, 2009, 182: 5723-5729.