Cutting edge: generation of memory precursors and functional memory CD8+ T cells depends on T cell factor-1 and lymphoid enhancer-binding factor-1
X Zhou, HH Xue - The Journal of Immunology, 2012 - journals.aai.org
X Zhou, HH Xue
The Journal of Immunology, 2012•journals.aai.orgAbstract 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 …
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 …
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.
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