{Reference Type}: Journal Article
{Title}: Plasticity and lineage commitment of individual TH1 cells are determined by stable T-bet expression quantities.
{Author}: Hegazy AN;Peine C;Niesen D;Panse I;Vainshtein Y;Kommer C;Zhang Q;Brunner TM;Peine M;Fröhlich A;Ishaque N;Marek RM;Zhu J;Höfer T;Löhning M;
{Journal}: Sci Adv
{Volume}: 10
{Issue}: 23
{Year}: 2024 Jun 7
{Factor}: 14.957
{DOI}: 10.1126/sciadv.adk2693
{Abstract}: T helper 1 (TH1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated TH1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the TH2 lineage: T-bet quantities were inversely correlated with the ability to express the TH2 lineage-specifying transcription factor GATA-3 and TH2 cytokines. Reprogramed TH1 cells acquired graded mixed TH1 + TH2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated TH1 cells was essential to ensure TH1 cell stability. Thus, innate cytokine signals regulate TH1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.