Division-linked generation of death-intermediates regulates the numerical stability of memory CD8 T cells

Jeffrey C. Nolz, Deepa Rai, Vladimir P. Badovinac, John T. Harty

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Infection or successful vaccination results in the formation of long-lived memory CD8 T-cell populations. Despite their numerical stability, memory CD8 T-cell populations are thought to completely turn over through proliferation within a 2- to 3-mo period. Therefore, steady-state memory cell proliferation must be balanced by a precisely regulated and equivalent death rate. However, the mechanisms regulating this balancing process remain completely undefined. Herein, we provide evidence for "death-intermediate memory cells" (TDIM) within memory CD8 T-cell populations generated by infection. Importantly, CD62L Lo/CD27 LoT DIMs are functionally characterized by an inability to produce cytokines, the failure to internalize T-cell receptor following antigenic stimulation, and signatures of apoptotic death. Furthermore, we demonstrate that, mechanistically, T DIM are directly generated from dividing "central memory" T-cell populations undergoing memory turnover in vivo. Collectively, these results demonstrate that as central memory CD8 T cells proliferate, they continuously generate a population of CD8 T cells that are nonfunctional and apoptotic; thus, our data support a model wherein division-linked generation of T DIM contributes to numerically stable CD8 T-cell memory.

Original languageEnglish (US)
Pages (from-to)6199-6204
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number16
DOIs
StatePublished - Apr 17 2012

ASJC Scopus subject areas

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