Ghiasi H, Wechsler S L, Cai S, Nesburn A B, Hofman F M
Ophthalmology Research, Cedars-Sinai Research Institute, Los Angeles, CA; Department of Ophthalmology, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Immunology. 1998 Nov;95(3):352-9. doi: 10.1046/j.1365-2567.1998.00602.x.
In order to determine the possible correlation of specific immune responses with protection against mortality and ocular disease following ocular herpes simplex virus type 1 (HSV-1) challenge, BALB/c mice were vaccinated with different doses and regimens of baculovirus-expressed gD. Neutralizing antibody, virus titres in the eyes, corneal scarring, and survival were measured. In addition, infiltration into the cornea of CD4+ T cells and cells containing the lymphokines interleukin-2 (IL-2), IL-4, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were monitored on days 3, 7, 10, 14 and 21 post-challenge by immunocytochemistry. The vaccination regimens used induced varying degrees of immune responses and protection upon ocular challenge with HSV-1. Our results suggest that neutralizing antibody was the most important immune response in protecting mice against lethal ocular challenge and corneal scarring. TNF-alpha and IL-2 were not crucial in terms of survival and corneal scarring, since gD1 (one vaccination with 1 microg of gD) and gD0.1 (one vaccination with 0.1 microg of gD), both of which provided high levels of protection, showed no TNF-alpha or IL-2 expression. However, TNF-alpha and IL-2 were crucial in terms of virus clearance from the eyes, since gD3 (three vaccinations with 1 microg of gD), which had less virus in their eyes, had high numbers of TNF-alpha and IL-2 infiltrates. Finally, mock-vaccinated mice were not protected from death and corneal disease following HSV-1 challenge. Eyes of mock-vaccinated mice had little or no TNF-alpha or IL-2 responses and the strongest IL-4 and IL-6 responses.
为了确定特定免疫反应与单纯疱疹病毒1型（HSV-1）眼部攻击后抗死亡和眼部疾病保护之间的可能相关性，用不同剂量和方案的杆状病毒表达的gD对BALB/c小鼠进行疫苗接种。测量了中和抗体、眼中的病毒滴度、角膜瘢痕形成和存活率。此外，在攻击后第3、7、10、14和21天，通过免疫细胞化学监测CD4+T细胞以及含有细胞因子白细胞介素-2（IL-2）、IL-4、IL-6和肿瘤坏死因子-α（TNF-α）的细胞向角膜的浸润情况。所使用的疫苗接种方案在用HSV-1进行眼部攻击后诱导了不同程度的免疫反应和保护作用。我们的结果表明，中和抗体是保护小鼠免受致命性眼部攻击和角膜瘢痕形成的最重要免疫反应。就存活和角膜瘢痕形成而言，TNF-α和IL-2并非关键因素，因为提供高水平保护的gD1（单次接种1μg gD）和gD0.1（单次接种0.1μg gD）均未显示TNF-α或IL-2表达。然而，就从眼中清除病毒而言，TNF-α和IL-2至关重要，因为眼中病毒较少的gD3（三次接种1μg gD）有大量的TNF-α和IL-2浸润。最后，假接种的小鼠在HSV-1攻击后未受到死亡和角膜疾病的保护。假接种小鼠的眼睛几乎没有或没有TNF-α或IL-2反应，而IL-4和IL-6反应最强。
