T-bet

Szabo, Glimcher 2000

T-cell specific transcription factor from the family of T-box genes encoded by the TBX21 gene on chromosome 17. The formative part of this transcription factor is a highly conserved sequence called 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 by 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 signaling cascade is initiated by activation of the T cell receptor and STAT-1. This leads to an increased expression of T-bet. T-bet not only controls the production of IFN-γ, but also influences the Th2 cells in a kind of inverse feedback loop.

The functional knock-out of the T-bet gene leads to a very weak production of IFN-γ when CD4 cells are stimulated under conditions that induce a Th1 response, but to a significant increase in Th2 cytokines such as IL4 and IL-5.

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

1. Domeier PP et al (2016) IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity. J Exp Med 213:715-732.
2. Elbendary A et al (2016) Expression of T-bet and GATA-3 in early mycosis fungoides and spongiotic dermatitis. J Am Acad Dermatol 74:1012-1014.
3. Hosokawa H et al (2016) Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells. Nat Commun 7:11289.
4. Szabo SJ et al (2000) A novel transcription factor, T-bet, directs Th1 linear commitment. Cell 100: 655-669.