Endothelial immune surveillance by intravascular antigen-experienced CD8(+) T cells as a novel mechanism of antiviral adaptive immunity

Abstract Following acute infection, pathogen-specific CD8+ T cells proliferate and divide in a heterogeneous manner, giving rise to effector and memory T cells with distinct migratory patterns. This migratory division of labor ensures that the host is efficiently scanned for ongoing or recurring infections. Recent evidence suggests that the presumed migratory behavior of the classical effector memory T cell subset needs revision. Here, we report that terminally differentiated effector and effector memory T cells adhere to and patrol the endothelium, while less differentiated T cells migrate into peripheral tissues. Interestingly, patrolling T cells have been observed at vascular beds such as the dermal microvasculature, where they concentrate in arterioles and preferentially migrate against the blood flow. Patrolling T cells survey the endothelium in the search for cognate antigen and, once encountered, cease their migration and establish long-lived interactions with peptide-presenting endothelial cells without inducing cytotoxicity. Finally, single-cell RNA-Seq analysis of patrolling CD8+ T effector cells and blockade experiments to prevent patrolling have unveiled a key and unexpected role for patrolling in the generation and maintenance of the intravascular CD8+ CX3CR1high KLRG-1+ effector memory T cell subset, which in turn is relevant for long-term protective immunity.