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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,...

. 2020 ; 21 (12) : 1552-1562. [pub] 20201012

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21011804

Grantová podpora
C17199/A18246/A29202 Cancer Research UK - United Kingdom
100326/Z/12/Z Wellcome Trust - United Kingdom

E-zdroje Online Plný text

NLK ProQuest Central od 2000-07-01 do Před 1 rokem
Health & Medicine (ProQuest) od 2000-07-01 do Před 1 rokem
Public Health Database (ProQuest) od 2000-07-01 do Před 1 rokem

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

Innovative Immunotherapies Unit Division of Immunology Transplantation and Infectious Diseases IRCCS San Raffaele Scientific Institute Milan Italy

Institute of Genetic and Biomedical Research UoS Milan National Research Council Rozzano Milan Italy

Laboratory of Translational Immunology Humanitas Clinical and Research Center IRCCS 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

Unit of Clinical and Experimental Immunology Humanitas Clinical and Research Center IRCCS Rozzano Milan Italy

University of Regensburg Regensburg Germany

Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research Center Seattle WA USA

Citace poskytuje Crossref.org

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