T-bet

Szabo, Glimcher 2000

T-cell-specific transcription factor from the T-box gene family, which is encoded by the TBX21 gene (TBX21 stands for: T-box transcription factor 21) on chromosome 17. The defining part of this transcription factor is a highly conserved sequence called the T-box . T-bet acts as the key regulator of the Th1 response and is responsible for controlling the production of IFN-gamma . It is controlled via a negative feedback mechanism with IFN-gamma.

When a naive CD4 T lymphocyte recognizes an antigen (e.g. a pathogenic germ) in the presence of IFN-gamma, a coordinated signalling cascade is set in motion via the activation of the T cell receptor and STAT1. This leads to increased expression of T-bet. This induces the formation of IL12 with consecutive activation of STAT-4. T-bet not only controls the production of IFN-gamma, but also influences the Th2 cells in a kind of inverse feedback loop.

Functional silencing of the coding TBX21 gene leads to a very low production of IFN-gamma when CD4 cells are stimulated under conditions that elicit a Th1 response, but to a significant increase in Th2 cytokines such as IL4 and IL5.

The master regulator of the Th2 response, on the other hand, is GATA 3. The balance between T-bet and GATA3 is important for a balanced immune response. Disturbances of this homeostasis are observed in various diseases. Disorders of this homeostasis are observed in various diseases, such as type I allergies and numerous autoimmune diseases.

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5. Szabo SJ et al. (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655-669.
6. Yang R et al. (2020) Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria. Cell 183:1826-1847