Effector-like CD8+ T Cells in the Memory Population Mediate Potent Protective Immunity

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199 Scopus citations

Abstract

The CD8+ memory Tcell population is heterogeneous, and it is unclear which subset(s) optimally mediate the central goal of the immune system-protection against infection. Here we investigate the protective capacities of CD8+ Tcell subsets present at the memory stage of the immune response. We show that a population of CD8+ Tcells bearing markers associated with effector cells (KLRG1hi, CD27lo, T-bethi, Eomeslo) persisted to the memory phase and provided optimal control of Listeria monocytogenes and vaccinia virus, despite weak recall proliferative responses. After antigen-specific boosting, this population formed the predominant secondary memory subset and maintained superior pathogen control. The effector-like memory subset displayed a distinct pattern of tissue distribution and localization within the spleen, and their enhanced capacity to eliminate Listeria involved specialized utilization of cytolysis. Together, these data suggest that long-lived effector CD8+ Tcells are optimal for protective immunity against certain pathogens.

Original languageEnglish (US)
Pages (from-to)1250-1260
Number of pages11
JournalImmunity
Volume38
Issue number6
DOIs
StatePublished - Jun 27 2013

Bibliographical note

Funding Information:
We thank the Masopust laboratory (especially Kristin Anderson) for help establishing splenic localization assays and timely provision of aged memory P14 CD8 + T cells, Josiah Zacharias for valuable experimental input, and the University of Minnesota Flow Core personnel for cell sorting. We are grateful to Kris Hogquist, Matt Mescher, Dave Masopust, Dietmar Zehn, Stephen McSorley, and members of the Jamequist laboratory for mouse and bacterial strains and helpful discussions. This work was supported by the National Institutes of Health (grants R01AI75168 and R37AI38903 to S.C.J., and Cancer Biology Postdoctoral Training Grant 5T32CA009138-38 to J.A.O) and a Leukemia and Lymphoma Career Development Award (to S.E.H.).

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