CD137 costimulation is associated with reduced herpetic stromal keratitis and with developing normal CD8+ T cells in trigeminal ganglia.
CD137 costimulation is associated with reduced herpetic stromal keratitis and with developing normal CD8+ T cells in trigeminal ganglia.
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CD137 共刺激与疱疹性基质角膜炎的减少以及三叉神经节中正常 CD8 T 细胞的发育有关。
DOI：
10.1099/jgv.0.001756
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Stuart,PatrickM
中科院分区：
文献类型：
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作者：
Yin,Xiao-Tang;Baugnon,NicholasK;Krishnan,Rohini;Potter,ChloeA;Yarlagadda,Sudha;Keadle,TammieL;Stuart,PatrickM
共刺激相互作用在发展对感染性病原体的免疫反应方面可能是至关重要的。我们最近报道，单纯疱疹病毒1型(HSV-1)感染的角膜需要有功能的CD28-CD80/86相互作用，以不仅降低脑炎的可能性，而且还介导病毒重新激活后的疱疹间质角膜炎(HSK)。本着同样的精神，我们决定确定CD137共刺激在HSK中所起的作用。使用B6-CD137L-/-小鼠，以及CD137的拮抗性和激动型抗体，我们表征了免疫反应以及CD137在此疾病中发挥的重要作用程度。在病毒形成潜伏感染的角膜和三叉神经节中都测量了免疫反应。我们证明了CD137共刺激可以减少角膜疾病。有趣的是，我们观察到缺乏CD137共刺激导致CD8+T细胞在三叉神经节的扩张和功能显著降低。最后，我们发现，经过基因改造表达CD137的病毒显著减少了角膜疾病，尽管它们在潜伏感染重新激活后确实出现了类似水平的三叉神经感染和外周病毒产生。CD137的相互作用导致HSK减少，是形成强大的三叉神经CD8+T细胞反应所必需的。
Costimulatory interactions can be critical in developing immune responses to infectious agents. We recently reported that herpes simplex type 1 (HSV-1) infections of the cornea require a functional CD28-CD80/86 interaction to not only reduce the likelihood of encephalitis, but also to mediate herpetic stromal keratitis (HSK) following viral reactivation. In this same spirit we decided to determine the role that CD137 costimulation plays during HSK. Using both B6-CD137L-/-mice, as well as antagonistic and agonistic antibodies to CD137 we characterize the immune response and to what extent CD137 plays an important role during this disease. Immune responses were measured in both the cornea and in the trigeminal ganglia where the virus forms a latent infection. We demonstrate that CD137 costimulation leads to reduced corneal disease. Interestingly, we observed that lack of CD137 costimulation resulted in significantly reduced CD8+T expansion and function in the trigeminal ganglia. Finally, we showed that viruses that have been genetically altered to express CD137 display significantly reduced corneal disease, though they did present similar levels of trigeminal infection and peripheral virus production following reactivation of a latent infection. CD137 interactions lead to reduced HSK and are necessary to develop robust trigeminal CD8+T cell responses.