Progressive telomere shortening of Epstein-Barr virus-specific memory T cells during HIV infection: Contributor to exhaustion?

Progressive telomere shortening of Epstein-Barr virus-specific memory T cells during HIV infection: Contributor to exhaustion?
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DOI:
10.1086/592170
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发表时间:
2008-11-01
影响因子:
6.4
通讯作者:
Akbar, Arne N.
Akbar, Arne N.
中科院分区:
医学2区
文献类型:
--
作者:
van Baarle, Debbie;Nanlohy, Nening M.;Akbar, Arne N.

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感染人类免疫缺陷病毒(HIV)的个体在面对高EBV负荷时具有低数量的功能性EB病毒(EBV)特异性CD8(+)T细胞,这表明这些细胞已经耗尽。我们研究了HIV感染期间观察到的慢性EBV负荷是否会导致EBV特异性T细胞的耗竭,方法是使用流式细胞术结合荧光原位杂交分析EBV特异性CD8(+)T细胞的端粒长度。在HIV感染期间,观察到EBV特异性T细胞的端粒缩短增强,而在健康受试者的CD8(+)T细胞中观察到端粒长度下降。因此,长期暴露于高抗原水平可能导致抗原特异性T细胞端粒的进行性缩短,这可能损害病毒控制。
Individuals infected with human immunodeficiency virus (HIV) have low numbers of functional Epstein-Barr virus (EBV)-specific CD8(+) T cells in the face of a high EBV load, suggesting that these cells have become exhausted. We investigated whether the observed chronic EBV loads during HIV infection could cause exhaustion of EBV-specific T cells by using flow-FISH (flow cytometry in combination with fluorescence in situ hybridization) to analyze the telomere length of EBV-specific CD8(+) T cells. Enhanced telomere shortening of EBV-specific T cells was observed during HIV infection, compared with the decline in telomere length observed in the CD8(+) T cells of healthy subjects. Thus, chronic exposure to high antigen levels may lead to the progressive shortening of telomeres of antigen-specific T cells, which may impair viral control.