Differential activation of human lung epithelial cell subsets by virus-specific CD8⁺ T cell derived IFNg

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B124
Abstract ID: 5064

Presenting Author:
Cameron L.R. Mattingly , Graduate Student at Emory Univ. Sch. of Med.

Abstract:

Lung CD8+ tissue resident memory T cells (TRM) act as sentinels that rapidly respond to respiratory viruses. While mouse models have shown that TRM mediate protection at barrier sites, our understanding in human lungs remains limited. We examined the functionality of virus-specific CD8+ TRM from non-transplantable, healthy human lungs by first quantifying their frequency and phenotype against prevalent viruses. While CD8+ T cells targeting respiratory viruses displayed a heightened tissue residency profile, RNAseq revealed that Flu and CMV specific lung CD8+ T cells are functionally and transcriptionally similar. Next, we investigated how virus-specific CD8s impact cells in the local lung environment. Following antigen stimulation, we noted activation of both innate and epithelial cells, dependent on IFNg. Examination of epithelial subsets showed that basal cells were more activated than ciliated cells. Upon stimulating lung CD8+ TRM with flu peptide +/- anti-IFNg, we conducted scRNAseq on epithelial cells and observed that stimulated CD8+ TRM robustly activated anti-viral genes in basal cells and to a lesser degree in secretory cells. Using Air-Liquid Interface (ALI) cultures, we modeled the effects of IFNg mediated epithelial activation on viral replication. Our findings show how crosstalk between CD8+ TRM and respiratory epithelium activates ISG pathways in epithelial cells and by doing so significantly decreases the frequency of infection and overall viral load.