[HTML][HTML] Quantifying memory CD8 T cells reveals regionalization of immunosurveillance

EM Steinert, JM Schenkel, KA Fraser, LK Beura… - Cell, 2015 - cell.com
EM Steinert, JM Schenkel, KA Fraser, LK Beura, LS Manlove, BZ Igyártó, PJ Southern…
Cell, 2015cell.com
Memory CD8 T cells protect against intracellular pathogens by scanning host cell surfaces;
thus, infection detection rates depend on memory cell number and distribution. Population
analyses rely on cell isolation from whole organs, and interpretation is predicated on
presumptions of near complete cell recovery. Paradigmatically, memory is parsed into
central, effector, and resident subsets, ostensibly defined by immunosurveillance patterns
but in practice identified by phenotypic markers. Because isolation methods ultimately inform …
Summary
Memory CD8 T cells protect against intracellular pathogens by scanning host cell surfaces; thus, infection detection rates depend on memory cell number and distribution. Population analyses rely on cell isolation from whole organs, and interpretation is predicated on presumptions of near complete cell recovery. Paradigmatically, memory is parsed into central, effector, and resident subsets, ostensibly defined by immunosurveillance patterns but in practice identified by phenotypic markers. Because isolation methods ultimately inform models of memory T cell differentiation, protection, and vaccine translation, we tested their validity via parabiosis and quantitative immunofluorescence microscopy of a mouse memory CD8 T cell population. We report three major findings: lymphocyte isolation fails to recover most cells and biases against certain subsets, residents greatly outnumber recirculating cells within non-lymphoid tissues, and memory subset homing to inflammation does not conform to previously hypothesized migration patterns. These results indicate that most host cells are surveyed for reinfection by segregated residents rather than by recirculating cells that migrate throughout the blood and body.
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