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

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

Preview

PDF - Published Version Available under License Creative Commons Attribution Non-commercial. Download (1MB) | Preview

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
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

Citation Data

Cited 16 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item