Strang G, Rickinson A B
Eur J Immunol. 1987 Jul;17(7):1007-13. doi: 10.1002/eji.1830170717.
Primary Epstein-Barr virus (EBV) infection, when manifest as infectious mononucleosis (IM), induces a broad-ranging and apparently non-HLA-restricted cytotoxic response whose nature has not been resolved. In the present experiments the ability to cryo-preserve IM mononuclear cell preparations, after depletion of CD16+ natural killer cells, has allowed detailed analysis of the response on appropriately constructed target cell panels. The results show that IM effector preparations are polyclonal with separate HLA class I antigen-dependent reactivities against the autologous EBV-transformed lymphoblastoid cell line (LCL) and particular HLA class I-mismatched LCLs. The autologous LCL-directed response shows the hallmarks of immunologically specific T cell cytotoxicity; only EBV+ B cell blasts are recognized and the interaction can be blocked by monoclonal antibodies to CD3 and CD8 on the effector cell surface and to HLA class I antigens on the target cell. Such findings demonstrate, for the first time, that the primary cytotoxic response to EBV infection includes a virus-specific HLA-restricted component like that found in the T cell memory of persistently infected individuals. Separate components of the response are preferentially active against some (but not all) HLA-mismatched LCLs, the pattern of reactivity being distinct for each individual IM patient and reproducible on repeated testing. Monoclonal antibody blocking experiments show that these HLA-mismatched interactions also involve CD3 and CD8 antigens on the effector cell and HLA class I antigens on the target cell. Where tested, such lysis affected both EBV+ and EBV- B cell blasts from the relevant HLA-mismatched donors. We postulate that a widespread primary infection of the B cell system by EBV leads to a generalized expansion not just of the virus-specific response but also of other T cell responses coincidentally active at the time. The unusual activity of IM effector preparations against HLA-mismatched LCLs arises from fortuitous cross-recognition of allogeneic cells by immunologically specific cytotoxic T cell clones coincidentally expanded in vivo alongside the EBV-specific response.
原发性爱泼斯坦-巴尔病毒（EBV）感染若表现为传染性单核细胞增多症（IM），会引发广泛且明显不受人类白细胞抗原（HLA）限制的细胞毒性反应，其本质尚未明确。在本实验中，在去除CD16 + 自然杀伤细胞后对IM单核细胞制剂进行冷冻保存的能力，使得能够在适当构建的靶细胞板上详细分析该反应。结果表明，IM效应制剂是多克隆的，对自体EBV转化的淋巴母细胞系（LCL）和特定的HLA I类抗原不匹配的LCL具有独立的HLA I类抗原依赖性反应性。针对自体LCL的反应显示出免疫特异性T细胞细胞毒性的特征；仅识别EBV + B细胞母细胞，并且效应细胞表面的抗CD3和CD8单克隆抗体以及靶细胞上的HLA I类抗原可阻断这种相互作用。这些发现首次证明，对EBV感染的原发性细胞毒性反应包括病毒特异性HLA限制成分，类似于在持续感染个体的T细胞记忆中发现的成分。反应的不同成分对某些（但不是全部）HLA不匹配的LCL具有优先活性，每个IM患者的反应模式各不相同，并且在重复测试中可重现。单克隆抗体阻断实验表明，这些HLA不匹配的相互作用也涉及效应细胞上的CD3和CD8抗原以及靶细胞上的HLA I类抗原。在进行测试的情况下，这种裂解影响来自相关HLA不匹配供体的EBV + 和EBV - B细胞母细胞。我们推测，EBV对B细胞系统的广泛原发性感染不仅导致病毒特异性反应的普遍扩展，还导致当时同时活跃的其他T细胞反应的扩展。IM效应制剂对HLA不匹配LCL的异常活性源于在体内与EBV特异性反应同时扩展的免疫特异性细胞毒性T细胞克隆对异基因细胞的偶然交叉识别。
