IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.

Abstract:

:Long-living memory stem T cells (T(SCM)) 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(+) T(SCM) lymphocytes starting from naive 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, T(SCM) 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 naive and central memory cells. When transplanted in immunodeficient mice, gene-modified naive-derived T(SCM) 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 T(SCM) are the only T-cell subset able to expand and mediate GVHD on serial transplantation, suggesting self-renewal capacity in a clinically relevant setting. These findings provide novel insights into the origin and requirements for T(SCM) generation and pave the way for their clinical rapid exploitation in adoptive cell therapy.

journal_name

Blood

journal_title

Blood

authors

Cieri N,Camisa B,Cocchiarella F,Forcato M,Oliveira G,Provasi E,Bondanza A,Bordignon C,Peccatori J,Ciceri F,Lupo-Stanghellini MT,Mavilio F,Mondino A,Bicciato S,Recchia A,Bonini C

doi

10.1182/blood-2012-05-431718

subject

Has Abstract

pub_date

2013-01-24 00:00:00

pages

573-84

issue

4

eissn

0006-4971

issn

1528-0020

pii

blood-2012-05-431718

journal_volume

121

pub_type

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