title: Cutting edge: generation of memory precursors and functional memory CD8+ T cells depends on T cell factor-1 and lymphoid enhancer-binding factor-1.
abstract: 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-7Rα+ 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-γ, granzyme B, and perforin, they were defective in TNF-α 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.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. xinyuan.zhou@gmail.com
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Hai-Hui
authors.initials: HH
authors.lastname: Xue
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D008089:Listeria monocytogenes / Q000276:immunology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D051822:T Cell Transcription Factor 1 / Q000172:deficiency / Q000502:physiology*
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051822:T Cell Transcription Factor 1