自然杀伤细胞可防止单纯疱疹病毒1型在眼部从前向后直接扩散。

Natural killer cells prevent direct anterior-to-posterior spread of herpes simplex virus type 1 in the eye.

作者信息

Tanigawa M, Bigger J E, Kanter M Y, Atherton S S

机构信息

Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 78229-3900, USA.

出版信息

Invest Ophthalmol Vis Sci. 2000 Jan;41(1):132-7.

PMID:10634612

Abstract

PURPOSE

Anterior chamber (AC) inoculation of the KOS strain of herpes simplex virus type 1 (HSV-1) results in morphologic sparing of the ipsilateral retina, whereas the retina of the uninoculated contralateral eye becomes infected and undergoes acute retinal necrosis. Natural killer (NK) cells are an important component of the primary immune response to most virus infections. The purpose of this study was to determine whether NK cells are involved in preventing early direct anterior-to-posterior spread of HSV-1 after AC inoculation.

METHODS

Normal BALB/c mice were inoculated with 4 X 10(4) plaque-forming units (PFU) of the KOS strain of HSV-1 using the AC route. NK activity was measured in the spleen, the superficial cervical and submandibular lymph nodes, and the inoculated eye by lysis of chromium-labeled, NK-sensitive YAC-1 target cells. Histopathologic scoring and immunohistochemical staining for HSV-1 were performed in NK-depleted (injected intravenously with anti-asialo GM1) or mock-depleted (injected intravenously with normal rabbit serum) mice.

RESULTS

In mock-depleted mice, NK activity in the spleens, superficial cervical and submandibular lymph nodes, and inoculated eyes peaked at postinoculation (pi) day 5 and declined by pi day 7. Treatment with anti-asialo GM1 eliminated NK activity in the eye and at nonocular sites. The histopathologic scores at pi day 5 indicated more damage to the retinas of NK-depleted mice than to those of mock-depleted mice, and immunohistochemical staining for HSV-1 showed spread of the virus to the sensory retina only in NK-depleted mice.

CONCLUSIONS

NK cells were activated within 5 days after AC inoculation of the KOS strain of HSV-1. Activation of NK cells appears to play a role in preventing direct anterior-to-posterior spread of the virus in the inoculated eye which, in turn, protects the retina of this eye and helps to explain why the architecture of the retina of this eye is spared.

摘要

目的

向眼前房（AC）接种1型单纯疱疹病毒（HSV-1）的KOS株会使同侧视网膜在形态上得以保留，而未接种的对侧眼视网膜则会被感染并发生急性视网膜坏死。自然杀伤（NK）细胞是对大多数病毒感染的主要免疫反应的重要组成部分。本研究的目的是确定NK细胞是否参与预防AC接种后HSV-1早期从前向后的直接扩散。

方法

使用AC途径向正常BALB/c小鼠接种4×10⁴空斑形成单位（PFU）的HSV-1 KOS株。通过裂解铬标记的、对NK敏感的YAC-1靶细胞，在脾脏、颈浅淋巴结和下颌下淋巴结以及接种眼中测量NK活性。对NK细胞耗竭（静脉注射抗去唾液酸GM1）或模拟耗竭（静脉注射正常兔血清）的小鼠进行HSV-1的组织病理学评分和免疫组织化学染色。

结果

在模拟耗竭的小鼠中，脾脏、颈浅淋巴结和下颌下淋巴结以及接种眼中的NK活性在接种后（pi）第5天达到峰值，并在pi第7天下降。抗去唾液酸GM1处理消除了眼中和非眼部部位的NK活性。pi第5天的组织病理学评分表明，NK细胞耗竭小鼠的视网膜损伤比模拟耗竭小鼠的更严重，HSV-1的免疫组织化学染色显示病毒仅在NK细胞耗竭的小鼠中扩散到感觉视网膜。