Pro-Inflammatory Cytokines Control The Anti-Viral Nk Cell Response.
| dc.contributor.advisor | Sun, Joseph | |
| dc.contributor.author | Madera, Sharline | |
| dc.date.accessioned | 2019-03-26T15:29:18Z | |
| dc.date.available | 2019-03-27T06:01:05Z | |
| dc.date.issued | 2015 | |
| dc.description.abstract | Although natural killer (NK) cells are considered part of the innate immune system, recent studies have demonstrated the capability of virus-specific NK cells to become long-lived and contribute to potent recall responses similar to T and B cells. The precise signals that promote the generation of a long-lived NK cell response are largely undefined. This dissertation investigates the role of pro-inflammatory cytokines interleukin (IL)-12, IL-18, and type I IFN on the NK cell response during mouse cytomegalovirus (MCMV) infection. We demonstrate that IL-12 and its signaling component STAT4 are indispensible for MCMV-specific NK cell expansion and generation of “memory” NK cells in lymphoid and non-lymphoid tissues. Furthermore, IL-12 and STAT4 signaling in activated NK cells increased the expression of the adaptor protein MyD88, which mediates signaling downstream of the IL-18 receptor, and T-box transcription factor T-bet. During MCMV infection, NK cells required IL-18 receptor and MyD88 for optimal primary expansion, but not recall responses. In addition, NK cell-specific deletion of T-bet or Eomes crippled the anti-viral NK cell response. Lastly, we show type I IFN and STAT1 signaling protects NK cells form NKG2D-mediated killing, thus promoting a robust antiviral NK cell response. This work highlights the complex, non-redundant, and stage-specific role of pro-inflammatory cytokines and transcription factors on the NK cell response. | |
| dc.identifier.uri | https://hdl.handle.net/1813/64649 | |
| dc.language.iso | en_US | |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | MCMV | |
| dc.subject | memory | |
| dc.subject | natural killer cells | |
| dc.subject | pro-inflammatory cytokines | |
| dc.subject | T-box transcription factors | |
| dc.subject | viral infection | |
| dc.title | Pro-Inflammatory Cytokines Control The Anti-Viral Nk Cell Response. | |
| dc.type | dissertation or thesis | |
| thesis.degree.discipline | Immunology & Microbial Pathogenesis | |
| thesis.degree.grantor | Weill Cornell Graduate School of Medical Sciences | |
| thesis.degree.level | Doctor of Philosophy |
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