Identification of cytomegalovirus-specific cytotoxic T lymphocytes in vitro is greatly enhanced by the use of recombinant virus lacking the US2 to US11 region or modified vaccinia virus Ankara expressing individual viral genes
Identification of cytomegalovirus-specific cytotoxic T lymphocytes in vitro is greatly enhanced by the use of recombinant virus lacking the US2 to US11 region or modified vaccinia virus Ankara expressing individual viral genes
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DOI：
10.1128/jvi.79.5.2869-2879.2005
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Moss, PAH
中科院分区：
文献类型：
--
作者：
Khan, N;Bruton, R;Moss, PAH
巨细胞病毒（CMV）在人体内引起一种强有力的T细胞反应，似乎可以保护宿主免受病毒相关疾病的侵害。尽管面临强大的宿主防御机制，CMV仍然是一种终身感染，可能会重新激活并导致免疫功能低下个体的危及生命的疾病。这种持久性可能是由属于US基因家族的基因编码的病毒的免疫颠覆蛋白的表达所辅助的。这些蛋白质调节感染细胞中主要组织相容性复合物的表达，并使体外实验偏向于仅检测某些特异性。我们结合使用重组CMV，缺乏US 2到US 11区域基因，和细胞质γ干扰素染色，以确定一个更准确的评估CMV特异性反应在体内。重组CMV刺激揭示了在所有测试的供体中比亲本病毒大得多的CD 8应答。在某些情况下，这表示检测到的细胞数量增加了10倍。大多数捐助者的反应主要针对pp 65、IE-1和pp 50。此外，在少数病例中可以检测到以前未报告的IE-2特异性T细胞应答。此外，我们观察到在一些供体中，CD 4 T细胞对突变型CMV的应答增加不太明显。这表明体内存在比用野生型病毒再刺激所揭示的更广泛的对CMV的T细胞应答，并增加了免疫逃避策略的功效可能不像以前认为的那样绝对的证据。
Cytomegalovirus (CMV) elicits a potent T-cell response in humans that appears to protect the host from virus-associated disease. Despite facing strong host defense mechanisms, CMV remains as a lifelong infection that may reactivate and cause life-threatening disease in immunocompromised individuals. This persistence is probably assisted by expression of immune subversion proteins of the virus encoded by genes belonging to the US gene family. These proteins modulate major histocompatibility complex expression in infected cells and bias in vitro experiments toward the detection of only certain specificities. We have combined the use of recombinant CMV, lacking the US2 to US11 region genes, and cytoplasmic gamma interferon staining to define a more accurate assessment of CMV-specific responses in vivo. Recombinant CMV stimulation reveals a CD8 response much larger than that of parental virus in all donors tested. In some cases, this represented up to 10-fold increases in the number of cells detected. Responses were directed mainly against pp65, IE-1, and pp50 in the majority of donors. In addition, previously unreported IE-2-specific T-cell responses could be detected in a minority of cases. Furthermore, we observed a less marked increase in the response to mutant CMV by CD4 T cells in some donors. This suggests that a much broader T-cell response to CMV exists in vivo than is revealed by restimulation with wild-type virus and adds to the evidence that the efficacy of immune evasion strategies may not be as absolute as previously believed.