Long-living memory stem T cells (TSCM) with the ability to self-renew and the plasticity to differentiate into potent effectors could be valuable weapons in adoptive T-cell therapy against cancer. Nonetheless, procedures to specifically target this T-cell population remain elusive. Here we show that it is possible to differentiate in vitro, expand and gene modify in clinically compliant conditions CD8+ TSCM lymphocytes starting from naïve precursors. Requirements for the generation of this T-cell subset, described as CD62L+CCR7+CD45RA+CD45R0+IL- 7Rα+CD95+, are CD3/CD28 engagement and culture with IL-7 and IL-15. Accordingly TSCM accumulates early after hematopoietic stem cell transplantation. The gene expression signature and functional phenotype define this population as a distinct memory T lymphocyte subset, intermediate between naïve and central memory cells. When transplanted in immunodeficient mice, gene-modified naïve-derived TSCM prove superior to other memory lymphocytes for the ability to expand and differentiate into effectors able to mediate a potent xenogeneic GvHD. Furthermore, gene-modified TSCM are the only T-cell subset able to expand and mediate GvHD upon serial transplantation, suggesting self-renewal capacity in a clinically relevant setting. These findings provide novel insights into the origin and requirements for TSCM generation and pave the way for their clinical rapid exploitation in adoptive cell therapy

IL-7 and IL-15 instruct the generation of human memory stem T cells from naïve precursors / N., Cieri; B., Camisa; Cocchiarella, Fabienne; Forcato, Mattia; G., Oliveira; E., Provasi; A., Bondanza; C., Bordignon; J., Peccatori; F., Ciceri; M. T., Lupo Stanghellini; Mavilio, Fulvio; A., Mondino; Bicciato, Silvio; Recchia, Alessandra; C., Bonini. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 121(2013), pp. 573-584.

I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Powered by IRIS-about IRIS-Utilizzo dei cookie

 Copyright © 2021