CD8 +T RM-derived IFNγ is a critical activator of human lung epithelial cells.

Abstract Due to their position in the pulmonary mucosa, CD8 +tissue resident memory T cells (T RM) act as sentinels that rapidly respond to, and mediate protection against, respiratory viruses. In mice, RMhave been shown at barrier sites by producing cytokines, chemokines, performing cell lysis. However, humans, less is known about effector functions of virus-specific lung +T RM. Using from healthy human donors, we first identified quantified frequency antigen-specific against common viruses intracellular cytokine staining. We next investigated polyfunctionality residency profiles responding found CD69 +CD103 RMcomprise a larger portion for largely restricted epithelium when compared specific with broader tissue tropism. Next, series vitro peptide stimulation neutralization experiments, how impact local innate epithelial cells. When stimulated cognate antigen, RM-derived IFNγ strongly correlated activation. Finally, RMwith antigen +/− anti-IFNγ performed RNAseq on RM(CD25 +CD137 +) determine exactly alters cellular program these Results this study suggest RMact reprogram immune cells, data will ultimately help us understand RMfit into overall response This project supported R35 HL150803 Emory Center Excellence Influenza Research Response (CEIRR) 75N93019R0028.