Infection of APC by human cytomegalovirus controlled through recognition of endogenous nuclear immediate early protein 1 by specific CD4+ T lymphocytes
Infection of APC by human cytomegalovirus controlled through recognition of endogenous nuclear immediate early protein 1 by specific CD4+ T lymphocytes
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DOI：
10.4049/jimmunol.169.3.1293
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发表时间：
2002-08-01
影响因子：
4.4
通讯作者：
Davignon, JL
中科院分区：
文献类型：
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作者：
Le Roy, E;Baron, M;Davignon, JL
人CMV感染受细胞免疫应答控制。专职APC如单核细胞和巨噬细胞可以在体内感染，并被认为是病毒的储存库。然而，CMV特异性的CD 4（+）对感染的APC的反应还没有报道。为了建立一个CD 4感染的APC相互作用的模型，我们用11类反式激活因子（CIITA）转染了U373 MG星形细胞瘤细胞系。共聚焦显微镜实验表明，U373 MG-CIITA细胞表达APC的特征性标志物。功能分析表明，感染的U373 MG-CIITA APC处理和提出外源性和内源性新合成的核立即早期（IE）蛋白1通过MHC类If途径。更重要的是，感染的APC对IE 1的内源性呈递导致CMV感染的有效控制，如通过降低的病毒滴度所揭示的。因此，这些结果描述了通过MHC 11类途径内源性呈递核病毒蛋白，并表明IE 1特异性CD 4（+）T细胞可能通过直接作用于受感染的APC在CMV感染中发挥重要作用。
Infections by human CMV are controlled by cellular immune responses. Professional APC such as monocytes and macrophages can be infected in vivo and are considered as a reservoir of virus. However, CMV-specific CD4(+) responses against infected APC have not been reported. To develop a model of CD4-infected APC interaction, we have transfected the U373MG astrocytoma cell line with the class 11 transactivator (CIITA). Confocal microscopy experiments showed that U373MG-CIITA cells expressed markers characteristic of APC. Functional assays demonstrated that infected U373MG-CIITA APC processed and presented both exogenous and endogenously neosynthesized nuclear immediate early (IE) protein 1 through the MHC class If pathway. More importantly, endogenous presentation of IE1 by infected APC lead to efficient control of CMV infection as revealed by decreased viral titer. Thus, these results describe the endogenous presentation of a nuclear viral protein by the MHC class 11 pathway and suggest that IE1-specific CD4(+) T cells may play an important role in CMV infection by directly acting against infected APC.