A Dapl1 + subpopulation of naïve CD8 T cells is enriched for memory-lineage precursors
Year: 2025
Type: article
Abstract: Memory CD8 T cells provide long-lasting immunity, but their developmental origins remain incompletely defined. Growing evidence suggests that functional heterogeneity exists within the naïve T cell pool, shaping lineage potential before antigen stimulation. Here, we identify a subpopulation of naïve CD8 T cells expressing death-associated protein-like 1 (Dapl1) that contains preprogrammed precursors biased toward memory differentiation. The differentiation of these precursors is independent of Dapl1 but relies on the transcription factor B-cell lymphoma/leukaemia 11b (Bcl11b), resulting in the generation of Dapl1 + central memory–like CD8 T cells after infection and stem-like memory cells in cancer. Dapl1 + naïve T cells originate among mature thymocytes and gradually appear in the periphery postnatally. Peripheral Dapl1 + and Dapl1 − populations show limited plasticity, supporting a thymic-imprinting model. These findings reveal a developmentally imprinted subset of naïve CD8 T cells committed to memory fate, uncovering an alternative pathway for memory T cell generation offering new avenues for therapeutic application.
Source: Science Advances
Institution: University of Massachusetts Amherst
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: Defining the role of let-7 miRNAs in the differentiation of exhausted and memory T cells, G5001766, Cellular Engineering Biotechnology Training Program, Defining post-transcriptional mechanisms that control CD8 T cell longevity, proliferation and differentiation, Production and Validation of monoclonal antibodies to enhance rigor and reproducibility in research vertebrate animal model
OpenAlex ID: W4413419001