MULTIPLE HLA CLASS-I-DEPENDENT CYTOTOXICITIES CONSTITUTE THE NON-HLA-RESTRICTED RESPONSE IN INFECTIOUS-MONONUCLEOSIS
MULTIPLE HLA CLASS-I-DEPENDENT CYTOTOXICITIES CONSTITUTE THE NON-HLA-RESTRICTED RESPONSE IN INFECTIOUS-MONONUCLEOSIS
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DOI：
10.1002/eji.1830170717
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发表时间：
1987-07-01
影响因子：
5.4
通讯作者：
RICKINSON, AB
中科院分区：
文献类型：
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作者：
STRANG, G;RICKINSON, AB
原发性 Epstein-Barr 病毒 (EBV) 感染，当表现为传染性单核细胞增多症 (IM) 时，会诱发广泛且明显非 HLA 限制的细胞毒性反应，其性质尚未得到解决。在目前的实验中，在去除 CD16+ 自然杀伤细胞后冷冻保存 IM 单核细胞制剂的能力允许详细分析对适当构建的靶细胞组的反应。结果表明，IM 效应器制剂是多克隆的，具有针对 (a) 自体 EBV 转化的淋巴母细胞系 (LCL) 和 (b) 特定 HLA I 类不匹配 LCL 的独立 HLA I 类抗原依赖性反应性。自体 LCL 定向反应显示了免疫特异性 T 细胞细胞毒性的标志；仅识别 EBV+ B 细胞母细胞，并且可以通过针对效应细胞表面上的 CD3 和 CD8 以及针对靶细胞上的 HLA I 类抗原的单克隆抗体来阻断相互作用。这些发现首次证明，EBV 感染的主要细胞毒性反应包括病毒特异性 HLA 限制成分，就像在持续感染个体的 T 细胞记忆中发现的那样。反应的单独成分优先针对某些（但不是全部）HLA 不匹配的 LCL 起作用，每个 IM 患者的反应模式是不同的，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 错配相互作用还涉及效应细胞上的 CD3 和 CD8 抗原以及靶细胞上的 HLA I 类抗原。经过测试，这种裂解影响了来自相关 HLA 不匹配供体的 EBV+ 和 EBV- B 细胞母细胞。我们假设 EBV 对 B 细胞系统的广泛初次感染不仅会导致病毒特异性反应的普遍扩展，还会导致当时同时激活的其他 T 细胞反应的普遍扩展。 IM 效应制剂针对 HLA 不匹配的 LCL 的异常活性源于免疫特异性细胞毒性 T 细胞克隆对同种异体细胞的偶然交叉识别，这些克隆与 EBV 特异性反应同时在体内扩增。
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 to appropriately constructed target cell panels. The results show that IM effector preparations are polyclonal with separate HLA class I antigen-dependent reactivities against (a) the autologous EBV-transformed lymphoblastoid cell line (LCL) and (b) 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 patterns 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 activae 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 cytoctoxic T cell clones coincidentally expanded in vivo alongside the EBV-specific response.