ArticlebioRxiv : the preprint server for biology2025
Functional heterogeneity and plasticity in naïve CD8 T cells drive superior effector and memory responses.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
While significant progress has been made in defining subsets among antigen-experienced CD8 T cells, the heterogeneity of naïve CD8 T cells remains poorly understood. Here, we identify naïve CD8 T cell subsets with superior persistence and an enhanced capacity to generate effector and memory cells, leading to more effective protection. These high-quality naïve CD8 T cells are marked by IL-18Rα, CD73, and CXCR3, and functionally less potent naïve CD8 T cells can convert into these superior subsets. Their enhanced response to infections is driven by better survival of the progeny effector cells during the T cell expansion phase. This improved survival is mediated by increased Ly6C2 expression on effector cells derived from these high-quality naïve cells. Collectively, our findings reveal functional heterogeneity and plasticity among naïve CD8 T cells and uncover a mechanism by which high-quality naïve subsets drive robust CD8 T cell responses, providing a previously unrecognized layer of immune regulation.
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