Cutting Edge: Generation of Memory Precursors and Functional Memory CD8+ T Cells Depends on T Cell Factor-1 and Lymphoid Enhancer-Binding Factor-1

T cell factor (TCF)-1 and lymphoid enhancer-binding factor (LEF)-1 transcription factors have redundant roles in promoting thymocyte maturation. TCF-1 has been recently shown to critically regulate memory CD8(+) T cell differentiation and persistence. The complete spectra of regulatory roles for TCF-1 and LEF-1 in CD8(+) T cell responses are yet unknown. We conditionally targeted LEF-1, and by combination with germline deletion of TCF-1, we found that loss of both factors completely abrogated the generation of KLR G1(lo)IL-7R alpha(+) memory precursors in effector CD8(+) T cell populations in response to Listeria monocytogenes infection. Whereas CD8(+) effectors deficient for TCF-1 and LEF-1 retained the capacity to express IFN-gamma, granzyme B, and perforin, they were defective in TNF-alpha production. In the memory phase, the Ag-specific CD8(+) T cells lacking TCF-1 and LEF-1 exhibited an effector phenotype and were severely impaired in secondary expansion upon rechallenge. Thus, TCF-1 and LEF-1 cooperatively regulate generation of memory precursors and protective memory CD8(+) T cells. The Journal of Immunology, 2012, 189: 2722-2726.