Central memory CD8⁺ T cells (Tcm) control systemic secondary infections and can protect from chronic infection and cancer as a result of their stem-cell-like capacity to expand, differentiate, and self-renew. Central memory is generally thought to emerge following pathogen clearance and to form based on the de-differentiation of cytolytic effector cells. Here, we uncovered rare effector-phase CD8⁺ T cells expressing high amounts of the transcription factor Tcf7 (Tcf1) that showed no evidence of prior cytolytic differentiation and that displayed key hallmarks of Tcm cells. These effector-phase Tcf7^hi cells quantitatively yielded Tcm cells based on lineage tracing. Mechanistically, Tcf1 counteracted the differentiation of Tcf7^hi cells and sustained the expression of conserved adult stem-cell genes that were critical for CD8⁺ T cell stemness. The discovery of stem-cell-like CD8⁺ T cells during the effector response to acute infection provides an opportunity to optimize Tcm cell formation by vaccination.

中央记忆CD8 ⁺ T细胞（Tcm）控制全身性继发感染，并且由于它们具有干细胞样的扩增，分化和自我更新能力，因此可以预防慢性感染和癌症。通常认为中枢记忆是在病原体清除后出现，并基于溶细胞效应细胞的去分化而形成。在这里，我们发现了罕见的效应期CD8 ⁺ T细胞，其表达大量的转录因子Tcf7（Tcf1），这些转录因子未显示出先前的细胞溶解分化的迹象，并且显示了Tcm细胞的关键特征。这些效应相Tcf7 ^hi细胞基于谱系追踪定量产生Tcm细胞。从机制上讲，Tcf1抵消了Tcf7 ^hi细胞并持续表达对于CD8 ⁺ T细胞干性至关重要的保守成人干细胞基因。在效应物对急性感染的效应反应期间，干细胞样CD8 ⁺ T细胞的发现为通过疫苗接种优化Tcm细胞形成提供了机会。