Key Points
IL-7Rαlow EM CD8+ T cells are anergy-like cells in vivo.
IL-7Rαlow EM CD8+ T cells are defective in aerobic glycolysis.
Visual Abstract
Abstract
Effector memory (EM) CD8+ T cells expressing lower levels of IL-7R α (IL-7Rαlow) from healthy individuals are partly compromised in vitro, but the identity of these cells has remained unclear. In this study, we demonstrate that human IL-7Rαlow EM CD8+ T cells are naturally occurring anergic cells in vivo and impaired in proliferation and IL-2 production but competent in IFN-γ and TNF-α production, a state that can be restored by IL-2 stimulation. IL-7Rαlow EM CD8+ T cells show decreased expression of GATA3 and c-MYC and are defective in metabolic reprogramming toward glycolysis, a process required for the proliferation of T cells. However, IL-7Rαlow EM CD8+ T cells can proliferate with TCR stimulation in the presence of IL-2 and IL-15, suggesting that these cells can be restored to normality or increased activity by inflammatory conditions and may serve as a reservoir for functional immunity.
Footnotes
This work was supported in part by the Creative Pioneering Researcher’s Program through Seoul National University (800-2020049 to H.-R.K.), by the SK Telecom Research Fund (3420130260 to H.-R.K.), by the Korea Healthcare Technology Research and Development Project of the Korea Health Industry Development Institute of the Ministry for Health, Welfare, and Family Affairs (HI17C0534 to H.-R.K.), and by the Interdisciplinary Research Initiatives Program from College of Engineering and College of Medicine, Seoul National University (800-20190263 to H.-R.K.).
The sequences presented in this article have been submitted to the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) under accession numbers GSE89576 and GSE89577.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- CCK-8
- Cell Counting Kit-8
- DEG
- differentially expressed gene
- ECAR
- extracellular acidification rate
- EM
- effector memory
- GATA3
- GATA binding protein 3
- GEO
- Gene Expression Omnibus
- GSEA
- Gene Set Enrichment Analysis
- KEGG
- Kyoto Encyclopedia of Genes and Genomes
- Lck
- lymphocyte-specific protein tyrosine kinase
- 2-NBDG
- 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose
- NUAK1
- novel (nua) kinase family 1
- OCR
- oxygen consumption rate
- PLCγ1
- phospholipase C γ 1
- qPCR
- quantitative PCR
- siRNA
- small interfering RNA
- Tet
- tetramer
- TIL
- tumor-infiltrated lymphocyte
- TILN
- tumor-infiltrating lymph node.
- Received December 12, 2019.
- Accepted September 22, 2020.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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