Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Med. 2009 Jul;15(7):808-13. doi: 10.1038/nm.1982. Epub 2009 Jun 14.

Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells.

Author information

  • 1Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA. gattinol@mail.nih.gov

Abstract

Self-renewing cell populations such as hematopoietic stem cells and memory B and T lymphocytes might be regulated by shared signaling pathways. The Wnt-beta-catenin pathway is an evolutionarily conserved pathway that promotes hematopoietic stem cell self-renewal and multipotency by limiting stem cell proliferation and differentiation, but its role in the generation and maintenance of memory T cells is unknown. We found that induction of Wnt-beta-catenin signaling by inhibitors of glycogen sythase kinase-3beta or the Wnt protein family member Wnt3a arrested CD8(+) T cell development into effector cells. By blocking T cell differentiation, Wnt signaling promoted the generation of CD44(low)CD62L(high)Sca-1(high)CD122(high)Bcl-2(high) self-renewing multipotent CD8(+) memory stem cells with proliferative and antitumor capacities exceeding those of central and effector memory T cell subsets. These findings reveal a key role for Wnt signaling in the maintenance of 'stemness' in mature memory CD8(+) T cells and have major implications for the design of new vaccination strategies and adoptive immunotherapies.

Comment in

PMID:
19525962
[PubMed - indexed for MEDLINE]
PMCID:
PMC2707501
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk