{Reference Type}: Journal Article
{Title}: Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision.
{Author}: Abadie K;Clark EC;Valanparambil RM;Ukogu O;Yang W;Daza RM;Ng KKH;Fathima J;Wang AL;Lee J;Nasti TH;Bhandoola A;Nourmohammad A;Ahmed R;Shendure J;Cao J;Kueh HY;
{Journal}: Immunity
{Volume}: 57
{Issue}: 2
{Year}: 2024 Feb 13
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2023.12.006
{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. Mathematical modeling shows how this flexibility allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decisions ensure optimal immune responses against diverse threats.