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Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans
G. Galletti, G. De Simone, EMC. Mazza, S. Puccio, C. Mezzanotte, TM. Bi, AN. Davydov, M. Metsger, E. Scamardella, G. Alvisi, F. De Paoli, V. Zanon, A. Scarpa, B. Camisa, FS. Colombo, A. Anselmo, C. Peano, S. Polletti, D. Mavilio, L. Gattinoni,...
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
C17199/A18246/A29202
Cancer Research UK - United Kingdom
100326/Z/12/Z
Wellcome Trust - United Kingdom
NLK
ProQuest Central
from 2000-07-01 to 1 year ago
Health & Medicine (ProQuest)
from 2000-07-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-07-01 to 1 year ago
- MeSH
- Biomarkers MeSH
- Cell Differentiation immunology MeSH
- CD8-Positive T-Lymphocytes immunology metabolism MeSH
- Telomere Homeostasis MeSH
- Immunophenotyping MeSH
- Immunologic Memory * MeSH
- Humans MeSH
- Lymphoid Progenitor Cells cytology immunology metabolism MeSH
- Mice MeSH
- Gene Expression Profiling MeSH
- T-Lymphocyte Subsets immunology metabolism MeSH
- Computational Biology methods MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines.
Center for Cancer Research National Cancer Institute Bethesda MD USA
Center of Life Sciences Skolkovo Institute of Science and Technology Moscow Russia
Central European Institute of Technology Brno Czech Republic
Department of Biomedical Sciences Humanitas University Pieve Emanuele Milan Italy
Department of Medical Biotechnologies and Translational Medicine University of Milan Milan Italy
Division of Cancer and Genetics Cardiff University School of Medicine Cardiff UK
Division of Infection and Immunity Cardiff University School of Medicine Cardiff UK
Genomic Unit Humanitas Clinical and Research Center IRCCS Rozzano Milan Italy
Humanitas Flow Cytometry Core Humanitas Clinical and Research Center IRCCS Rozzano Milan Italy
Institute of Genetic and Biomedical Research UoS Milan National Research Council Rozzano Milan Italy
Pirogov Russian National Research Medical University Moscow Russia
Regensburg Center for Interventional Immunology Regensburg Germany
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry Moscow Russia
St Jude Children's Research Hospital Memphis TN USA
Systems Immunity Research Institute Cardiff University School of Medicine Cardiff UK
University of Regensburg Regensburg Germany
Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research Center Seattle WA USA
References provided by Crossref.org
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