Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory

• DOI: 10.1073/pnas.0914127107
• Publication Date: 2010-05-11T04:20:03Z
• Authors: Grégoire Jeannet; Caroline Boudousquié; Noémie Gardiol; Joonsoo Kang; Joerg Huelsken; Werner Held
• Keywords: Memory T cell

Immune protection from intracellular pathogens depends on the generation of terminally differentiated effector and multipotent memory precursor CD8 T cells, which rapidly regenerate cells during recurrent infection. The identification factors pathways involved in cell differentiation is obvious importance to improve vaccination strategies. Here, we show that mice lacking factor 1 (Tcf-1), a nuclear canonical Wingless/Integration (Wnt) signaling pathway, mount normal responses infection with lymphocytic choriomeningitis virus (LCMV). However, Tcf-1–deficient are selectively impaired their ability expand upon secondary challenge protect essentially lack evident already at peak primary response, suggesting Tcf-1 programs fate. function establish dependent catenin-binding domain requires coactivators Wnt intermediates β-catenin γ-catenin. These findings demonstrate pathway plays an essential role for central under physiological conditions vivo. They raise possibility modulation may be exploited or therapies designed promote sustained cytotoxic against tumors.