Journal
NATURE IMMUNOLOGY
Volume 21, Issue 5, Pages 567-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41590-020-0653-1
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Funding
- National Institutes of Health/National Cancer Institute F30 predoctoral fellowship [F30-CA236061, F30-CA217109]
- Univeristy of Chicago Medical Scientist Training Program [T32-GM007281]
- [R01-AI110507]
- [T32-AI007090]
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Savage and colleagues show virtual memory CD8 T cells arise in the thymus of replete mice, where their differentiation is a robust TCR-directed process. Clonal analyses show their TCR repertoire is reproducible and distinct from conventional cells and that progeny cells harboring such TCRs infiltrate tumors and express PD-1. Unprimed mice harbor a substantial population of 'memory-phenotype' CD8(+) T cells (CD8-MP cells) that exhibit hallmarks of activation and innate-like functional properties. Due to the lack of faithful markers to distinguish CD8-MP cells from bona fide CD8(+) memory T cells, the developmental origins and antigen specificities of CD8-MP cells remain incompletely defined. Using deep T cell antigen receptor (TCR) sequencing, we found that the TCRs expressed by CD8-MP cells are highly recurrent and distinct from the TCRs expressed by naive-phenotype CD8(+) T cells. CD8-MP clones exhibited reactivity to widely expressed self-ligands. T cell precursors expressing CD8-MP TCRs showed upregulation of the transcription factor Eomes during maturation in the thymus, prior to induction of the full memory phenotype, which is suggestive of a unique program triggered by recognition of self-ligands. Moreover, CD8-MP cells infiltrate oncogene-driven prostate tumors and express high densities of PD-1, which suggests potential roles in antitumor immunity and the response to immunotherapy.
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