Tonsillar homing of Epstein-Barr virus-specific CD8+ T cells and the virus-host balance
Tonsillar homing of Epstein-Barr virus-specific CD8+ T cells and the virus-host balance
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DOI：
10.1172/jci24810
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发表时间：
2005-09-01
影响因子：
15.9
通讯作者：
Rickinson, AB
中科院分区：
文献类型：
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作者：
Hislop, AD;Kuo, M;Rickinson, AB
经历原发性 EBV 感染的传染性单核细胞增多症 (IM) 患者血液中 EBV 特异性 CD8(+) T 细胞大量扩增。虽然 B 细胞池的潜伏感染很快得到控制，但口咽部裂解性感染细胞的病毒脱落量在几个月内仍然很高。因此，我们研究了在初次感染和持续存在期间，反应如何定位于扁桃体（EBV 的主要目标部位）。在急性IM中，与血液相比，扁桃体中的CD8+T细胞中EBV特异性效应器的代表性较差，这与这些高度活化的细胞上缺乏CCR7淋巴归巢标记物相一致。在最近从 IM 中恢复的患者中，潜在表位反应比裂解反应更快地获得 CCR7 并在扁桃体中积累，其中一些细胞现在表达 CD103 整合素，介导在粘膜部位的保留。相比之下，在溶解性和潜伏性感染都得到控制的长期病毒携带者中，与血液相比，扁桃体中溶解性表位反应性富集了2至5倍，潜伏性表位反应性富集了10至20倍；高达 20% 的扁桃体 CD8+ T 细胞具有 EBV 特异性，并且许多现在表达 CD 103。我们认为有效控制 EBV 感染需要适当的 CD8+ T 细胞归巢至口咽部位。
Patients with infectious mononucleosis (IM) undergoing primary EBV infection show large expansions of EBV-specific CD8(+) T cells in the blood. While latent infection of the B cell pool is quickly controlled, virus shedding from lytically infected cells in the oropharynx remains high for several months. We therefore studied how responses localize to the tonsil, a major target site for EBV, during primary infection and persistence. In acute IM, EBV-specific effectors were poorly represented among CD8(+) T cells in tonsil compared with blood, coincident with absence of the CCR7 lymphoid homing marker on these highly activated cells. In patients who had recently recovered from IM, latent epitope reactivities were quicker than lytic reactivities both to acquire CCR7 and to accumulate in the tonsil, with some of these cells now expressing the CD103 integrin, which mediates retention at mucosal sites. By contrast, in long-term virus carriers in whom both lytic and latent infections had been controlled, there was 2- to 5-fold enrichment of lytic epitope reactivities and 10- to 20-fold enrichment of latent epitope reactivities in tonsil compared with blood; up to 20% of tonsillar CD8(+) T cells were EBV specific, and many now expressed CD 103. We suggest that efficient control of EBV infection requires appropriate CD8(+) T cell homing to oropharyngeal sites.