The role of CD8+ T cells during the pre-clinical phase of corneal HSV-1 infection.

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dc.contributor.advisorSuvas, Susmit
dc.contributor.authorVohra, Ashima
dc.date.accessioned2014-02-04T16:04:55Z
dc.date.available2014-02-04T16:04:55Z
dc.date.issued2014-02-04
dc.description.abstractApproximately 90% of world’s population is seropositive for Herpes Simplex Virus-1 (HSV-1). However, most individuals show no symptoms because HSV-1 largely remains in its non-replicating mode inside the neurons. If the virus is activated, it can cause cold sores around the mouth. The virus can also migrate to the eye, where it causes infection and chronic inflammation in the cornea of the eye. The corneal inflammation induced by HSV-1, if not effectively controlled by steroids and anti-viral drugs, will then give rise to herpetic stromal keratitis (HSK). HSK leads to permanent corneal damage and is the leading cause of infection-induced blindness in the United States. If HSV-1 replication in the cornea continues to remain uncontrolled, the virus may spread to the brain and cause encephalitis (brain fever). In terms of HSV-1, CD8+ T cells are known to mediate viral latency in the neurons, but the role of this immune cell type in regulating corneal inflammation after ocular HSV-1 infection is not well characterized. In this study, we worked in a mouse model to decipher the role of CD8+ T cells in corneas infected with HSV-1. First, we measured the influx of CD8+ T cells in the cornea at different time points after ocular HSV-1 infection. Our preliminary data showed that CD8+ T cells are indeed present in HSV-1 infected corneas, with maximum levels on day 8 post-infection. Accordingly, we carried out localized depletion of CD8+ T cells in the cornea via subconjunctival administration of anti-CD8+ antibodies on day 5 and day 7 post-infection. The depletion of CD8+ T cells was confirmed by flow cytometry on day 9 post-infection. Interestingly, the loss of CD8+ T cells resulted in the development of encephalitis in approximately 50% of the treated mice, suggesting that the virus spread to the brain. To determine exactly how the loss of CD8+ T cells affects immunoinflammatory events in corneas infected with HSV-1, we carried out protein arrays for cytokines and angiogenic factors in the CD8+ depleted and non-depleted corneas. Our results indicated that, in the absence of CD8+ T cells, the levels of many pro-inflammatory cytokines, chemokines, and angiogenic factors were up-regulated in the cornea. As expected, the results of our experiments demonstrate the involvement of CD8+ T cells in the regulation of immunoinflammatory events in HSV-1 infected corneas. Future studies will be focused on determining how CD8+ T cells affect the development of HSK lesions.en_US
dc.identifier.urihttp://hdl.handle.net/10323/2635
dc.subjectHerpes simplex virusen_US
dc.subjectHerpetic stromal keratitisen_US
dc.subjectOcular infectionen_US
dc.subjectCorneaen_US
dc.subjectAngiogenesisen_US
dc.subjectCytokinesen_US
dc.subjectChemokinesen_US
dc.subjectInflammationen_US
dc.subjectImmunologyen_US
dc.subjectViral replicationen_US
dc.subjectLatencyen_US
dc.subjectPre-clinical phaseen_US
dc.subjectCD8+ T cellsen_US
dc.titleThe role of CD8+ T cells during the pre-clinical phase of corneal HSV-1 infection.en_US
dc.typeThesiseng

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