Graudate Student Emory Univ. Sch. of Med. Marietta, Georgia, United States
Disclosure(s):
Kirsten Kost: No financial relationships to disclose
Introduction/Rationale: CD8+ tissue-resident memory T cells (TRM) in the upper respiratory tract (URT) limit viral replication and prevent spread to the lower respiratory tract (LRT), where infection often causes significant morbidity and mortality. While long-term maintenance of URT TRM is essential for this protection, data demonstrating this feature and exploring mechanisms of maintenance is limited.
Methods: Using mouse models of intranasal and intraperitoneal vaccination, we show that URT CD8+ TRM can develop without local respiratory antigen, a feature distinguishing them from their LRT counterparts. Further, we demonstrate that URT TRM are maintained up to 8 months post-vaccination in both the presence and absence of local antigen, whereas LRT TRM experience gradual decline over time.
Results: To further elucidate the transcriptional cues governing long-term maintenance of URT TRM after parenteral vaccination, we performed bulk RNA sequencing 6 months post-intranasal and intraperitoneal priming. We are currently working to assess transcriptional patterns of URT TRM under these distinct antigen conditions. In addition, we are utilizing CD103-Cre reporter mice to track the contribution of effector memory cell recruitment or homeostatic proliferation in maintenance of the URT CD8+ TRM pool.
Conclusion: Our work aims to identify the mechanisms that regulate CD8+ TRM maintenance in the upper respiratory tract, offering valuable insights for T-cell-based vaccine strategies targeting respiratory viruses.
