Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells. Mus musculus

Tissue-resident memory T-cells (TRM) mediate optimal protection against respiratory infections. Little is known about human TRM. Here we characterized memory T-cells from human lungs. We identify two distinct memory T-cell populations in lung tissue. Lung TRM are poised for rapid, but restrained responsiveness by constitutive expression of genes encoding effector molecules and inhibitory regulators. Although TRM express little T-bet and Eomesodermin, transcription factor signatures revealed that multiple drivers of effector gene expression are active in TRM, including Notch. We show that Notch is required for maintenance of the CD103+ TRM population in mouse lungs. These findings suggests that the lung tissue environment actively maintains the T-cells that protect it from infectious assault through activating the Notch surface receptor in TRM. Overall design: From 18 mice, both CD69+ and CD69- memory T cells were taken, that were either treated with DMSO (control) or GSI, at time points 2 or 5 days.