Generation of memory precursors and functional memory CD8+ T cells depends on TCF-1 and LEF-1

摘要

TCF-1 and 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 spectrum 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 KLRG1^loIL-7Rα⁺ memory precursors in effector CD8⁺ T cell population 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 antigen-specific CD8⁺ T cells lacking TCF-1 and LEF-1 exhibited an effector phenotype and were severely impaired in secondary expansion upon re-challenge. Thus, TCF-1 and LEF-1 cooperatively regulate generation of memory precursors and protective memory CD8⁺ T cells.