Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance.

Memory CD8 T cells protect against intracellularpathogens by scanning host cell surfaces; thus,infection detection rates depend on memory cellnumber and distribution. Population analyses relyon cell isolation from whole organs, and interpreta-tion is predicated on presumptions of near completecell recovery. Paradigmatically, memory is parsedinto central, effector, and resident subsets, osten-sibly defined by immunosurveillance patterns but inpractice identified by phenotypic markers. Becauseisolation methods ultimately inform models ofmemory T cell differentiation, protection, and vac-cine translation, we tested their validity via parabi-osis and quantitative immunofluorescence micro-scopy of a mouse memory CD8 T cell population.We report three major findings: lymphocyte isolationfails to recover most cells and biases against certainsubsets, residents greatly outnumber recirculatingcells within non-lymphoid tissues, and memorysubset homing to inflammation does not conformto previously hypothesized migration patterns.These results indicate that most host cells are sur-veyed for reinfection by segregated residents ratherthan by recirculating cells that migrate throughoutthe blood and body.