Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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, 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

[img]
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: 21 Sep 2017 14:11
URI: http://orca.cf.ac.uk/id/eprint/104918

Citation Data

Cited 6 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics