Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision.

ABSTRACT: The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8⁺ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics, quantitative live imaging, and an acute infection model, we find that T cells will maintain or lose memory potential early after antigen recognition. However, following pathogen clearance, T cells may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by a stochastic cis-epigenetic switch that tunably and reversibly silences the memory regulator, TCF1, in response to stimulation. Mathem

SUBMITTER: Abadie K 

PROVIDER: S-EPMC10922671 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature