Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection
Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection
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DOI：
10.1182/blood-2003-06-1937
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发表时间：
2004-08-15
期刊：
影响因子：
20.3
通讯作者：
Riddell, SR
中科院分区：
文献类型：
--
作者：
Manley, TJ;Luy, L;Riddell, SR
虽然巨细胞病毒(CMV)表达的蛋白干扰I类主要组织相容性复合体(MHC)分子的抗原提呈，但CD8(+)细胞毒性T细胞(CTL)对于控制感染和维持潜伏期是不可或缺的。在这里，我们用细胞因子流式细胞术检测了免疫功能正常的CMV血清阳性个体中CD8(+)CTL的频率和特异性。CD8(+)CTL应答的很大一部分是针对病毒复制早期和早期阶段表达的病毒抗原，由感染RV798的成纤维细胞表达，而不是野生型CMV。这些结果表明，在体外观察到的对CMV感染细胞的I类抗原提呈的抑制不足以阻止体内自然感染后广泛的CD8(+)CTL的诱导。因此，通过细胞治疗或疫苗接种重建免疫缺陷患者的T细胞免疫可能需要靶向多种病毒抗原才能完全恢复对CMV的免疫控制。(C)2004年，由美国血液病学会提供。
Although cytomegalovirus (CMV) expresses proteins that interfere with antigen presentation by class I major histocompatibility complex (MHC) molecules, CD8(+) cytotoxic T cells (CTLs) are indispensable for controlling infection and maintaining latency. Here, a cytokine flow cytometry assay that employs fibroblasts infected with a mutant strain of CMV (RV798), which is deleted of the 4 viral genes that are responsible for interfering with class I MHC presentation, was used to examine the frequency and specificity of the CD8(+) CTLs to CMV in immunocompetent CMV-seropositive individuals. A large fraction of the CD8(+) CTL response was found to be specific for viral antigens expressed during the immediate early and early phases of virus replication and presented by fibroblasts infected with RV798 but not wild-type CMV. These results demonstrate that the inhibition of class I antigen presentation observed in CMV-infected cells in vitro is not sufficient to prevent the induction of a broad repertoire of CD8(+) CTLs after natural infection in vivo. Thus, reconstitution of T-cell immunity in immunodeficient patients by cell therapy or by vaccination may need to target multiple viral antigens to completely restore immunologic control of CMV. (C) 2004 by The American Society of Hematology.