The transcription factor Zfp335 promotes differentiation and persistence of memory CD8+ T cells by regulating TCF-1

Memory CD8+ T cells play an essential role in providing effective and lifelong protection against pathogens. Comprehensive transcriptional and epigenetic networks are involved in modulating memory T cell development, but the molecular regulations of CD8+ memory T cell formation and long-term persistence remain largely unknown. Here, we show that zinc finger protein 335 (Zfp335) is indispensable for CD8+ T cell memory establishment and maintenance during acute infections. Mice with Zfp335 deletion in CD8+ T cells exhibit a significant reduction of memory T cells and memory precursor cells in the contraction phase. WT and KO CD8+ T cells were sorted from the spleens of recipient mice 7 days after LM-OVA infection in the co-transfer model.