dc.creator | Rogers, Meredith Claire | |
dc.date.accessioned | 2020-08-24T11:52:26Z | |
dc.date.available | 2020-08-29 | |
dc.date.issued | 2018-08-29 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-08202018-153259 | |
dc.identifier.uri | http://hdl.handle.net/1803/15500 | |
dc.description.abstract | Viral respiratory infections, including infection by human metapneumovirus (HMPV), are associated with T cell impairment, wherein CD8+ T cells exhibit diminished production of cytokines and cytotoxic molecules. In this thesis I show that CD4+ regulatory T cells (Tregs) contribute to decreased CD8+ T cell function and impair clearance of HMPV. Additionally, I demonstrate a temporal role of Tregs in respiratory virus infection, where Tregs are essential during immune priming to promote cell migration and to control the balance of type 1 and type 2 immunity.
In this work, I also explored the role of the inhibitory ligand PD-L1 in T cell impairment. PD-L1 is the primary ligand that for the inhibitory receptor PD-1, and antibody blockade of PD-L1 restored CD8+ T cell function in T cell impairment. I found that paradoxically, however, mice genetically deficient in PD-L1 have even further reduced T cell function and antiviral immunity during respiratory virus infection.
Finally, I investigated the host species permissiveness of HMPV and found that this is limited by the virus’ capacity to antagonize the interferon signaling pathway of primates and mice. | |
dc.format.mimetype | application/pdf | |
dc.subject | regulatory t cell | |
dc.subject | pd-1 | |
dc.subject | inhibitory receptor | |
dc.subject | metapneumovirus | |
dc.subject | treg | |
dc.subject | lung | |
dc.subject | influenza | |
dc.subject | respiratory virus | |
dc.title | Immune regulation and evasion of acute respiratory virus infection | |
dc.type | dissertation | |
dc.contributor.committeeMember | Ambra Pozzi | |
dc.contributor.committeeMember | Terence Dermody | |
dc.contributor.committeeMember | Daniel Moore | |
dc.contributor.committeeMember | John V. Williams | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Microbiology and Immunology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2020-08-29 | |
local.embargo.lift | 2020-08-29 | |
dc.contributor.committeeChair | R. Stokes Peebles | |