Zanon, Veronica, Pilipow, Karolina, Scamardella, Eloise, De Paoli, Federica, De Simone, Gabriele, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Martinez Usatorre, Amaia, Romero, Pedro, Mavilio, Domenico, Roberto, Alessandra and Lugli, Enrico 2017. Curtailed T-cell activation curbs effector differentiation and generates CD8+ T cells with a naturally-occurring memory stem cell phenotype. European Journal of Immunology 47 (9) , pp. 1468-1476. 10.1002/eji.201646732 |
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Abstract
Human T memory stem (T SCM ) 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 + T-cell differentiation and allows the genera- tion of CD45RO – CD45RA + CCR7 + CD27 + CD95 + -phenotype cells from highly purified na ̈ ıve T-cell precursors, resembling naturally-occurring human T SCM . 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 ter- minal 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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Subjects: | R Medicine > R Medicine (General) |
Publisher: | John Wiley & Sons |
ISSN: | 0014-2980 |
Date of First Compliant Deposit: | 21 September 2017 |
Date of Acceptance: | 28 June 2017 |
Last Modified: | 04 May 2023 23:18 |
URI: | https://orca.cardiff.ac.uk/id/eprint/104918 |
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