Endothelial immune surveillance by intravascular antigen-experienced CD8+ T Cells: Uncovering an unrecognized role in antiviral defense 4519

Abstract Description Viral infections trigger CD8 T cell differentiation into phenotypically and functionally diverse effector cells. Biodistribution analysis revealed that terminally differentiated CX3CR1high T effectors are mostly confined to blood and excluded from the extravascular space in most tissues, what raised questions about their immunological function. By means of intravital multiphoton microscopy, we observed CX3CR1high T cells unceasingly surveilling dermal microvessels. This is a general phenomenon observed upon systemic and local infections, with multiple viral pathogens and using diverse entry portals. Unlike patrolling monocytes, CX3CR1high T effectors showed a profound directional bias, exhibiting rheotactic motility and being concentrated in arterioles. Interfering with their surveillance resulted in a selective loss of KLRG1+ T effector memory cells, highlighting the importance of patrolling in shaping the memory pool for long-term protective immunity. Moreover, recognition of cognate Ag on arterioles resulted in rapid arrest of patrolling T cells without eliciting cytotoxicity. Instead, they protect arterioles by secreting cytokines locally (among other signals) to trigger antiviral mechanisms in the endothelium that quell viral infection, preventing deleterious systemic dissemination. Without intravascular protection, these vascular segments ensheathed in a dense smooth muscle layer that prevents interaction with perivascular immune cells would become highly vulnerable. Funding Sources Supported by NIH 1R01AI155865: Differentiation of Antiviral Effector and Memory T Cell Subsets Topic Categories Viral Immunology (VIR)