An Evidence Audit of Phosphatidylserine Dynamics in CD8 T-cell Exhaustion: Defining the Remaining Experimental Gap

This research note presents an evidence audit of phosphatidylserine (PS) dynamics in CD8 T-cell exhaustion, with emphasis on the distinction between surface quantity, persistence, spatial organization, leaflet identity, and measurement limitations. The audit integrates primary-source review of key studies on PS exposure in acute and chronically stimulated CD8 T cells, including Fischer et al. (2006) and Medina et al. (2026), together with structured web searches and bibliographic-database searches in PubMed and Europe PMC conducted through 8 September 2026. A prespecified DIRECT criterion was used: a study had to directly measure the spatial distribution or spatiotemporal organization of exofacial PS in exhausted or chronically stimulated CD8 T cells. Flow-cytometric measures of PS abundance alone were not considered DIRECT evidence. No verified study meeting this criterion was identified within the searches performed. This is reported as a search result, not as proof that no such study exists. The audit further distinguishes reagent identity, binding specificity, and signal origin; evaluates probe-induced perturbation and extracellular-vesicle confounding; records unresolved aspects of PS persistence and spatial organization; and retains an explicit error log documenting claims that were corrected or withdrawn during the audit process. The principal unresolved question identified is whether the spatiotemporal organization of exofacial PS differs during the transition from acute activation to chronic stimulation/exhaustion. This document is an evidence audit / research note and does not propose a new therapeutic mechanism or intervention.