Amyes Elisabeth, Hatton Chris, Montamat-Sicotte Damien, Gudgeon Nancy, Rickinson Alan B, McMichael Andrew J, Callan Margaret F C
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, OX3 9DS Oxford, United Kingdom.
J Exp Med. 2003 Sep 15;198(6):903-11. doi: 10.1084/jem.20022058.
The CD8+ T cell response to Epstein-Barr virus (EBV) is well characterized. Much less is known about the evolution of the CD4+ T cell response. Here we show that EBV stimulates a primary burst of effector CD4+ T cells and this is followed by a period of down-regulation. A small population of EBV-specific effector CD4+ T cells survives during the lifelong persistent phase of infection. The EBV-specific effector CD4+ T cells accumulate within a CD27+ CD28+ differentiation compartment during primary infection and remain enriched within this compartment throughout the persistent phase of infection. Analysis of CD4+ T cell responses to individual epitopes from EBV latent and lytic cycle proteins confirms the observation that the majority of the effector cells express both CD27 and CD28, although CD4+ T cells specific for lytic cycle antigens have a greater tendency to express CD45RA than those specific for the latent antigens. In clear contrast, effector CD4+ T cells specific for cytomegalovirus (CMV) accumulate within the CD27- CD28+ and CD27- CD28- compartments. There are striking parallels in terms of the differentiation of CD8+ T cells specific for EBV and CMV. The results challenge current ideas on the definition of memory subsets.
针对爱泼斯坦-巴尔病毒（EBV）的CD8 + T细胞反应已得到充分表征。而对于CD4 + T细胞反应的演变了解较少。在此，我们表明EBV刺激效应性CD4 + T细胞的初次爆发，随后是一个下调期。一小部分EBV特异性效应性CD4 + T细胞在感染的终身持续阶段存活下来。在初次感染期间，EBV特异性效应性CD4 + T细胞在CD27 + CD28 +分化区室中积累，并在感染的持续阶段始终在该区域富集。对来自EBV潜伏和裂解周期蛋白的各个表位的CD4 + T细胞反应分析证实了以下观察结果：大多数效应细胞同时表达CD27和CD28，尽管针对裂解周期抗原的CD4 + T细胞比针对潜伏抗原的细胞更倾向于表达CD45RA。与之形成鲜明对比的是，针对巨细胞病毒（CMV）的效应性CD4 + T细胞在CD27 - CD28 +和CD27 - CD28 -区室中积累。针对EBV和CMV的CD8 + T细胞在分化方面存在显著的相似之处。这些结果对当前关于记忆亚群定义的观点提出了挑战。
