HTLV-1 cell lines differ in constitutively activated signaling pathways that can be altered by cytokine exposure

Examination of signaling pathways used by HTLV-1-infected rabbit cell lines revealed differences between one, RH/K30, that mediates asymptomatic infec tion and another, RH/K34, that causes lethal experimental leukemia. Both li nes are IL-2 independent; RH/K30 produces IL-4 while RH/K34 produces IL-10. Examination of the Jak/STAT (Janus kinase/signal transducer and activator of transcription) activation of the lines revealed constitutive phosphoryla tion of Jak1 in both. STAT6 phosphorylation, not previously reported for HT LV-1 cells, was observed in RH/K30; STAT1 and STAT3 were phosphorylated in RH/K34. Treatment with cytokines altered the activation of the STAT protein s: IL-2 induced STAT5 phosphorylation in both lines. Supernatant from RH/K3 4 or IL-10 induced STAT3 phosphorylation in RH/K30 cells. Supernatant from RH/K30 or IL-4 induced STAT6 phosphorylation in RH/K34 cells, which could b e reversed with a Jak kinase inhibitor-AG-490.