Quantifying memory CD8 T cells reveals regionalization of immunosurveillance

Elizabeth M. Steinert, Jason M. Schenkel, Kathryn A. Fraser, Lalit K. Beura, Luke S. Manlove, Botond Z. Igyártó, Peter J. Southern, David Masopust

Research output: Contribution to journalArticlepeer-review

316 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)737-749
Number of pages13
JournalCell
Volume161
Issue number4
DOIs
StatePublished - May 7 2015

Bibliographical note

Funding Information:
This work was supported by grants from the NIH (R01-AI084913 and R01-AI111671 to D.M., T32-AI083196 to E.M.S., F30-DK100159-02 to J.M.S., and F31-CA183226 to L.S.M.).

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