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- Title
Wnt signaling arrests effector T cell differentiation and generates CD8<sup>+</sup> memory stem cells.
- Authors
Gattinoni, Luca; Xiao-Song Zhong; Palmer, Douglas C.; Yun Ji; Hinrichs, Christian S.; Zhiya Yu; Wrzesinski, Claudia; Boni1, Andrea; Cassard, Lydie; Garvin, Lindsay M.; Paulos, Chrystal M.; Muranski, Pawel; Restifo, Nicholas P.
- 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–β-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–β-catenin signaling by inhibitors of glycogen sythase kinase-3β 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 CD44lowCD62LhighSca-1highCD122highBcl-2high 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.
- Publication
Nature Medicine, 2009, Vol 15, Issue 7, p808
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/nm.1982