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Updated: Sep 28, 2025

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Differential regulation of transcription factor T-bet induction during NK cell development and T helper-1 cell
Difeng Fang1, Kairong Cui2, Yaqiang Cao2
1Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Adaptive CD4+ T helper cells and their innate counterparts, innate lymphoid cells, utilize an identical set of transcription factors (TFs) for their differentiation and functions. However, similarities and differences in the induction of these TFs in related lymphocytes are still elusive. Here, we show that T helper-1 (Th1) cells and natural killer (NK) cells displayed distinct epigenomes at the Tbx21 locus, which encodes T-bet, a critical TF for regulating type 1 immune responses. The initial induction of T-bet in NK precursors was dependent on the NK-specific DNase I hypersensitive site Tbx21-CNS-3, and the expression of the interleukin-18 (IL-18) receptor; IL-18 induced T-bet expression through the transcription factor RUNX3, which bound to Tbx21-CNS-3. By contrast, signal transducer and activator of transcription (STAT)-binding motifs within Tbx21-CNS-12 were critical for IL-12-induced T-bet expression during Th1 cell differentiation both in vitro and in vivo. Thus, type 1 innate and adaptive lymphocytes utilize distinct enhancer elements for their development and differentiation.
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