Bickham Kara, Goodman Kiera, Paludan Casper, Nikiforow Sarah, Tsang Ming Li, Steinman Ralph M, Münz Christian
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
J Exp Med. 2003 Dec 1;198(11):1653-63. doi: 10.1084/jem.20030646.
The initiation of cell-mediated immunity to Epstein-Barr virus (EBV) has been analyzed with cells from EBV-seronegative blood donors in culture. The addition of dendritic cells (DCs) is essential to prime naive T cells that recognize EBV-latent antigens in enzyme-linked immunospot assays for interferon gamma secretion and eradicate transformed B cells in regression assays. In contrast, DCs are not required to control the outgrowth of EBV-transformed B lymphocytes from seropositive donors. Enriched CD4+ and CD8+ T cells mediate regression of EBV-transformed cells in seronegative and seropositive donors, but the kinetics of T-dependent regression occurs with much greater speed with seropositives. EBV infection of DCs cannot be detected by reverse transcription-polymerase chain reaction with primers specific for mRNA for the EBNA1 U and K exons. Instead, DCs capture B cell debris and generate T cells specific for EBV latency antigens. We suggest that the cross-presentation of EBV-latent antigens from infected B cells by DCs is required for the initiation of EBV-specific immune control in vivo and that future EBV vaccine strategies should target viral antigens to DCs.
利用培养的EB病毒（EBV）血清阴性献血者的细胞，对细胞介导的针对EBV免疫的启动情况进行了分析。在用于检测干扰素γ分泌的酶联免疫斑点试验中，添加树突状细胞（DC）对于激活识别EBV潜伏抗原的初始T细胞至关重要，并且在消退试验中可根除转化的B细胞。相比之下，控制血清阳性供体来源的EBV转化B淋巴细胞的生长则不需要DC。富集的CD4⁺和CD8⁺ T细胞介导血清阴性和血清阳性供体中EBV转化细胞的消退，但T细胞依赖性消退的动力学在血清阳性供体中发生得更快。用针对EBNA1 U和K外显子mRNA的特异性引物，通过逆转录-聚合酶链反应无法检测到DC被EBV感染。相反，DC捕获B细胞碎片并产生针对EBV潜伏抗原的T细胞。我们认为，DC对来自受感染B细胞的EBV潜伏抗原进行交叉呈递，是体内启动EBV特异性免疫控制所必需的，并且未来的EBV疫苗策略应将病毒抗原靶向DC。
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