JNK activation is transient in normal T cells but constitutive in ATL cells leading to permanent TGF-β1 resistance.

(Top) Stimulation of normal peripheral T cells induces JNK activity, leading to TGF-β1 production and preventing TGF-β1 inhibition through the induction of a Smad3/c-Jun complexes. This period may allow clonal expansion and triggering of the immune response. In normal T cells, JNK activation is transient and decreases after 72 to 96 hours, allowing TGF-β1 antiproliferative effect and restoration of a resting state. (Bottom) In contrast, in HTLV-1–transformed cells, Tax induces constitutive JNK activity that may lead to a continuous TGF-β1 resistance, allowing clonal expansion and a constitutively activated state observed in patients infected with HTLV-1. Subsequent oncogenic events associated with TGF-β1 resistance may result in ATL development.