%0 Journal Article
%T Plasticity and lineage commitment of individual TH1 cells are determined by stable T-bet expression quantities.
%A Hegazy AN
%A Peine C
%A Niesen D
%A Panse I
%A Vainshtein Y
%A Kommer C
%A Zhang Q
%A Brunner TM
%A Peine M
%A Fröhlich A
%A Ishaque N
%A Marek RM
%A Zhu J
%A Höfer T
%A Löhning M
%J Sci Adv
%V 10
%N 23
%D 2024 Jun 7
%M 38838155
%F 14.957
%R 10.1126/sciadv.adk2693
%X 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.