Innate immune control of EBV-infected B cells by invariant natural killer T cells
Innate immune control of EBV-infected B cells by invariant natural killer T cells
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DOI：
10.1182/blood-2013-01-480665
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发表时间：
2013-10-10
期刊：
影响因子：
20.3
通讯作者：
Tan, Rusung
中科院分区：
文献类型：
--
作者：
Chung, Brian K.;Tsai, Kevin;Tan, Rusung
患有X连锁淋巴组织增生性疾病的个体缺乏恒定的自然杀伤T（iNKT）细胞，并且对EB病毒（EBV）感染非常敏感。为了确定iNKT细胞是否识别或调节EBV，在存在或不存在iNKT细胞的情况下用EBV感染静息B细胞。iNKT细胞的消耗增加了病毒滴度和EBV感染的B细胞的频率。然而，EBV感染的B细胞迅速丧失iNKT细胞受体配体CD 1d的表达，从而废除iNKT细胞识别。为了确定诱导的CD 1d表达是否可以恢复EBV感染细胞中的iNKT识别，用AM 580处理淋巴母细胞样细胞系（LCL），AM 580是一种合成的视黄酸受体α激动剂，通过核蛋白淋巴增强子结合因子1（LEF-1）上调CD 1d表达。AM 580显著降低LEF-1在CD 1d启动子区的结合，诱导LCL上的CD 1d表达，并恢复LCL的iNKT识别。即使在没有外源性抗原的情况下，表达CD 1d的LCL也引起iNKT细胞的干扰素γ分泌和细胞毒性，表明内源性iNKT抗原在EBV感染期间表达。这些数据表明，iNKT细胞可能是重要的早期，先天控制B细胞感染的EBV和下调的CD 1d可能允许EBV绕过iNKT细胞介导的免疫识别。
Individuals with X-linked lymphoproliferative disease lack invariant natural killer T (iNKT) cells and are exquisitely susceptible to Epstein-Barr virus (EBV) infection. To determine whether iNKT cells recognize or regulate EBV, resting B cells were infected with EBV in the presence or absence of iNKT cells. The depletion of iNKT cells increased both viral titers and the frequency of EBV-infected B cells. However, EBV-infected B cells rapidly lost expression of the iNKT cell receptor ligand CD1d, abrogating iNKT cell recognition. To determine whether induced CD1d expression could restore iNKT recognition in EBV-infected cells, lymphoblastoid cell lines (LCL) were treated with AM580, a synthetic retinoic acid receptor-alpha agonist that upregulates CD1d expression via the nuclear protein, lymphoid enhancer-binding factor 1 (LEF-1). AM580 significantly reduced LEF-1 association at the CD1d promoter region, induced CD1d expression on LCL, and restored iNKT recognition of LCL. CD1d-expressing LCL elicited interferon gamma secretion and cytotoxicity by iNKT cells even in the absence of exogenous antigen, suggesting an endogenous iNKT antigen is expressed during EBV infection. These data indicate that iNKT cells may be important for early, innate control of B cell infection by EBV and that downregulation of CD1d may allow EBV to circumvent iNKT cell-mediated immune recognition.