Sullivan, Brooke
(2015)
STUDIES IN THE IMMUNE CONTROL OF HERPES SIMPLEX VIRUS TYPE 1 (HSV-1) LATENCY: THE ROLE OF CD4+ T CELLS AND IL-10 IN HSV-1 LATENCY.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Herpes simplex virus 1 (HSV-1) infection of the eye results in lytic viral replication in the corneal epithelium followed by a quiescent infection of the sensory neurons of the trigeminal ganglia (TG), which innervate the cornea. Reactivation of the HSV-1 from this latent state can result in pathologies, such as stromal keratitis in the eye and viral encephalitis. Currently, no therapeutics are available that eliminate latent HSV-1 infection or completely inhibit viral reactivation events. Development of more effective therapeutics to prevent HSV-1 reactivation and recurrent disease has been hindered by a lack of understanding of the immune mechanisms involved in maintaining viral latency and how they are controlled. CD8+ T cells are known to play multiple direct roles in preventing viral reactivation during latent HSV-1 infection, but a functional role for CD4+ T cells has not been established. Our current hypothesis is that CD4+ T cells present in the latent HSV-1-infected TG are a virus-specific, locally-activated population that regulates CD8+ T cell function through secretion of cytokines, such as IL-10 and IFN-γ, thereby influencing HSV-1 latency. Here, we provide data indicating that at least a portion of the CD4+ T cells in the TG during latency are HSV-specific and that they localize to defined APC populations in the latently infected TG. Our data also indicate that the numbers and functionality of CD8+ T cells that are specific for subdominant HSV-1 epitopes are regulated at least in part, by CD4+ T cells, through an IL-10-dependent mechanism.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
23 April 2015 |
| Date Type: |
Publication |
| Defense Date: |
20 April 2015 |
| Approval Date: |
23 April 2015 |
| Submission Date: |
21 April 2015 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
69 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Immunology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
CD8,
interleukin-10,
interferon gamma,
IFNγ,
Keratitis,
HSK,
Reactivation,
gB,
glycoprotein B,
gD,
glycoprotein D,
antigen specificity,
epitope,
peptide,
localization,
interactions,
F4/80,
Macrophage,
Dendritic cell,
DC,
Antigen presentation,
T cell activation,
Trigeminal ganglia,
TG,
Neuron,
CD8 exhaustion,
Persistent infection |
| Date Deposited: |
23 Apr 2015 12:18 |
| Last Modified: |
19 Dec 2016 14:42 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/25008 |
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