Letter abstract
Nature Medicine 15, 808 - 813 (2009)
Published online: 14 June 2009 | doi:10.1038/nm.1982
Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells
Luca Gattinoni1,2, Xiao-Song Zhong1,2, Douglas C Palmer1, Yun Ji1, Christian S Hinrichs1, Zhiya Yu1, Claudia Wrzesinski1, Andrea Boni1, Lydie Cassard1, Lindsay M Garvin1, Chrystal M Paulos1, Pawel Muranski1 & Nicholas P Restifo1
Self-renewing cell populations such as hematopoietic stem cells and memory B and T lymphocytes might be regulated by shared signaling pathways1. The Wnt–
-catenin pathway is an evolutionarily conserved pathway that promotes hematopoietic stem cell self-renewal and multipotency by limiting stem cell proliferation and differentiation2, 3, but its role in the generation and maintenance of memory T cells is unknown. We found that induction of Wnt–-catenin signaling by inhibitors of glycogen sythase kinase-3 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.
- Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
- These authors contributed equally to this work.
Correspondence to: Luca Gattinoni1,2 e-mail: gattinol@mail.nih.gov
Correspondence to: Nicholas P Restifo1 e-mail: restifo@nih.gov
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