Distinct transcriptomic signatures in pulmonary tissue resident and vascular resident-like T cells in nonhuman primates.

The concept of intravascular immunity is reshaping our understanding of immune surveillance, challenging the traditional view that immune responses are confined to either tissue parenchyma or the bloodstream. Our pilot study utilized intravascular staining (ivs) in rhesus macaques (RhM) to spatially distinguish pulmonary vasculature-associated (ivs+) CD8+ T cells from interstitial (ivs-) T cells. Single-cell RNA sequencing and flow cytometry revealed that ivs+ T cells are not passive blood contaminants but rather a distinct, "resident-like" population enriched in cytotoxic effectors, with elevated expression of transcripts associated with tissue residency, cell adhesion, and vascular/platelet interactions, while ivs- T cells exhibited a classic TRM signature. The presence of SIV-specific tetramer+ ivs+ CD8+ T cells in infected RhM suggests a role in antiviral defense within the lung vasculature. These findings provide new insight into intravascular immunity, highlighting a unique population of CD8+ T cells as potential pulmonary vascular sentinels poised for rapid immune responses.