Curtailed T-cell activation curbs effector differentiation and generates CD8<sup>+</sup> T cells with a naturally-occurring memory stem cell phenotype.

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Serval ID
serval:BIB_13B86EE92733
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Curtailed T-cell activation curbs effector differentiation and generates CD8<sup>+</sup> T cells with a naturally-occurring memory stem cell phenotype.
Journal
European journal of immunology
Author(s)
Zanon V., Pilipow K., Scamardella E., De Paoli F., De Simone G., Price D.A., Martinez Usatorre A., Romero P., Mavilio D., Roberto A., Lugli E.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
09/2017
Peer-reviewed
Oui
Volume
47
Number
9
Pages
1468-1476
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Human T memory stem (T <sub>SCM</sub> ) cells with superior persistence capacity and effector functions are emerging as important players in the maintenance of long-lived T-cell memory and are thus considered an attractive population to be used in adoptive transfer-based immunotherapy of cancer. However, the molecular signals regulating their generation remain poorly defined. Here we show that curtailed T-cell receptor stimulation curbs human effector CD8 <sup>+</sup> T-cell differentiation and allows the generation of CD45RO <sup>-</sup> CD45RA <sup>+</sup> CCR7 <sup>+</sup> CD27 <sup>+</sup> CD95 <sup>+</sup> -phenotype cells from highly purified naïve T-cell precursors, resembling naturally-occurring human T <sub>SCM</sub> . These cells proliferate extensively in vitro and in vivo, express low amounts of effector-associated genes and transcription factors and undergo considerable self-renewal in response to IL-15 while retaining effector differentiation potential. Such a phenotype is associated with a lower number of mitochondria compared to highly-activated effector T cells committed to terminal differentiation. These results shed light on the molecular signals that are required to generate long-lived memory T cells with potential application in adoptive cell transfer immunotherapy.
Keywords
Adult Stem Cells/physiology, Animals, Antigens, CD/metabolism, CD8-Positive T-Lymphocytes/physiology, Cancer Vaccines/immunology, Cell Differentiation, Cell Proliferation, Cell Self Renewal, Cells, Cultured, Humans, Immunologic Memory, Immunophenotyping, Immunotherapy, Adoptive/methods, Interleukin-15/metabolism, Lymphocyte Activation, Mice, Mice, SCID, Neoplasms/immunology, Neoplasms/therapy, Phenotype, Receptors, Antigen, T-Cell/metabolism, Adoptive cell transfer, CD8+, Effector T cells, T memory stem cells, T-cell activation
Pubmed
Web of science
Open Access
Yes
Create date
05/04/2018 9:53
Last modification date
21/08/2019 6:08
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