First Author | Zhou X | Year | 2010 |
Journal | Immunity | Volume | 33 |
Issue | 2 | Pages | 229-40 |
PubMed ID | 20727791 | Mgi Jnum | J:163912 |
Mgi Id | MGI:4830184 | Doi | 10.1016/j.immuni.2010.08.002 |
Citation | Zhou X, et al. (2010) Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity 33(2):229-40 |
abstractText | T cell factor 1 (TCF-1) is a transcription factor known to act downstream of the canonical Wnt pathway and is essential for normal T cell development. However, its physiological roles in mature CD8(+) T cell responses are unknown. Here we showed that TCF-1 deficiency limited proliferation of CD8(+) effector T cells and impaired their differentiation toward a central memory phenotype. Moreover, TCF-1-deficient memory CD8(+) T cells were progressively lost over time, exhibiting reduced expression of the antiapoptotic molecule Bcl-2 and interleukin-2 receptor beta chain and diminished IL-15-driven proliferation. TCF-1 was directly associated with the Eomes allele and the Wnt-TCF-1 pathway was necessary and sufficient for optimal Eomes expression in naive and memory CD8(+) T cells. Importantly, forced expression of Eomes partly protected TCF-1-deficient memory CD8(+) T cells from time-dependent attrition. Our studies thus identify TCF-1 as a critical player in a transcriptional program that regulates memory CD8 differentiation and longevity. |