Dcvelopment and migration of protective CD8+ T cells into the nervous system following ocular herpes simplex virus-1 infection
Dcvelopment and migration of protective CD8+ T cells into the nervous system following ocular herpes simplex virus-1 infection
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DOI：
10.4049/jimmunol.174.5.2919
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Nikolich-Zugich, J
中科院分区：
文献类型：
--
作者：
Lang, A;Nikolich-Zugich, J
在感染上皮细胞表面后，HSV-1引起多方面的抗病毒反应，控制病毒并将其限制在感觉神经节的潜伏期。这种反应包括CD8(+)T细胞，其确切作用(S)仍在确定；神经节的免疫监测和控制病毒传播到大脑被认为是关键作用。我们跟踪了眼部感染后淋巴组织和淋巴组织中CD8(+)T细胞反应的动态变化。HSV-1特异性CD8(+)T细胞最早出现在第5天的引流(下颌下)淋巴结中，从第6天开始在非引流的淋巴组织和淋巴外组织中均可检测到。然而，尽管淋巴器官中既有静止的(CD43(低)CFSE(高))细胞，也有处于不同增殖和激活阶段的病毒特异性细胞，但淋巴器官(眼、三叉神经节和脑)只包含经历8次以上增殖(CD43(高)CFSE(阴性))的激活细胞，并在与病毒AGS接触时迅速分泌干扰素-γ。不管激活状态如何，这些细胞似乎太晚了，无法阻止HSV-1的传播，早在可检测到的CD8(+)T细胞反应开始之前，就在眼睛(从第1天起)、三叉神经节(从第2天起)和脑(从第3天起)就可以看到这种情况。然而，从第6天开始，CD8(+)T细胞在减少病毒复制方面起着关键作用，并在第8天到第10天之间消除病毒；CD8缺陷动物未能控制病毒，在第6天后脑内表现出持续的高病毒滴度，并在第7天到第12天死于病毒性脑炎。因此，CD8(+)T细胞不控制HSV-1从初级组织到第三级组织的传播，而是攻击感染器官中的病毒，并控制其原位复制。
After infection of epithelial surfaces, HSV-1 elicits a multifaceted antiviral response that controls the virus and limits it to latency in sensory ganglia. That response encompasses the CD8(+) T cells, whose precise role(s) is still being defined; immune surveillance in the ganglia and control of viral spread to the brain were proposed as the key roles. We tracked the kinetics of the CD8(+) T cell response across lymphoid and extralymphoid tissues after ocular infection. HSV-1-specific CD8(+) T cells first appeared in the draining (submandibular) lymph node on day 5 and were detectable in both nondraining lymphoid and extralymphoid tissues starting on day 6. However, although lymphoid organs contained both resting (CD43(low)CFSE(high)) and virus-specific cells at different stages of proliferation and activation, extralymphoid sites (eye, trigeminal ganglion, and brain) contained only activated cells that underwent more than eight proliferations (CD43(high)CFSE(neg)) and promptly secreted IFN-gamma upon contact with viral Ags. Regardless of the state of activation, these cells appeared too late to prevent HSV-1 spread, which was seen in the eye (from day 1), trigeminal ganglia (from day 2), and brain (from day 3) well before the onset of a detectable CD8(+) T cell response. However, CD8(+) T cells were critical in reducing viral replication starting on day 6 and for its abrogation between days 8 and 10; CD8-deficient animals failed to control the virus, exhibited persisting high viral titers in the brain after day 6, and died of viral encephalitis between days 7 and 12. Thus, CD8(+) T cells do not control HSV-1 spread from primary to tertiary tissues, but, rather, attack the virus in infected organs and control its replication in situ.