dc.creator | Erickson, John Joseph | |
dc.date.accessioned | 2020-08-22T20:44:34Z | |
dc.date.available | 2016-12-03 | |
dc.date.issued | 2013-12-03 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-08072013-164449 | |
dc.identifier.uri | http://hdl.handle.net/1803/13847 | |
dc.description.abstract | My thesis project explores mechanisms controlling CD8+ T cell impairment in the lung during viral acute lower respiratory infection. I show that viral infection is required for lung T cell impairment and that cognate viral antigen recognized by the T cell receptor drives this process through the upregulation of inhibitory receptors. One such receptor, programmed death-1 (PD-1), is a key mediator of impairment during both primary infection and reinfection and prevents effective anti-viral immunity. Therapeutic blockade of the PD-1 pathway results in restored lung CD8+ T cell effector functions and enhances viral clearance without exacerbating lower airway pathology. Additionally, I show that PD-1 mediates CD8+ T cell dysfunction in a cell-intrinsic manner and further identify three additional inhibitory receptors that contribute to impairment. In particular, lymphocyte-activation gene 3 (LAG-3) rapidly compensates for loss of PD-1 signaling to return lung CD8+ T cells to an impaired state. In sum, I have elucidated mechanisms controlling lung CD8+ T cell impairment during viral acute lower respiratory infection, which have important implications for design of novel therapeutics and vaccine strategies against respiratory viruses. | |
dc.format.mimetype | application/pdf | |
dc.subject | PD-1 | |
dc.subject | impairment | |
dc.subject | CD8+ T cell | |
dc.subject | influenza virus | |
dc.subject | human metapneumovirus | |
dc.title | CD8+ T cells are impaired during viral acute respiratory infection by coordinated inhibitory pathways | |
dc.type | dissertation | |
dc.contributor.committeeMember | John V. Williams | |
dc.contributor.committeeMember | Ray S. Peebles | |
dc.contributor.committeeMember | Terence Dermody | |
dc.contributor.committeeMember | James Crowe | |
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 | 2016-12-03 | |
local.embargo.lift | 2016-12-03 | |
dc.contributor.committeeChair | Sebastian Joyce | |