Long-term maintenance of CD8+ tissue resident memory T cells in the upper respiratory tract 2257745

Abstract

Abstract Introduction 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. Funding Source NIH R35 HL150803; NIH F31 HL176090-02 Topic Categories Vaccines and Immunotherapy (VAC)