Molecular mechanisms of NF-κB mediated T-cell acitivation induced by HTLV-I Tax

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We examined the role of NF-κB in T-cell activation induced by the oncogene product Tax of human T-cell leukemia virus type I (HTLV-I).gp34 is a cell surface molecule which is expressed on antigen stimulated T-cells and HTLV-I infected T-cells, but not on mitogen stimulated T-cells. Consistent with this, NF-κB like sequence in gp34 promoter is activated by HTLV-I Tax, however it is not activated by TPA treatment unlike typical NF-κB which is activated by TPA treatment. For full understanding of molecular mechanism of T-cell activation by HTLV-I Tax, we have attempted to search for stimulation required for the activation of the NF-κB like sequence in addition to TPA treatment. We transfected gp34 promoter-driven luciferase plasmids into a human T-cell line Jurkat and examined whether the addition of ionomycin or antibodies against cell surface molecules (CD2, CD3, CD4, CD26 and CD28) enhanced reporter activity as compared to TPA treatment alone. Addition of ionomycin and anti-CD28 antibodies enhanced the reporter activity by 8 and 9 folds, respectively, indicating that the signaling pathways originated from increase in Ca concentration and CD28 can activate the gp34 NF-κB like sequence. However, the activation was lower than that by Tax (40 folds), indicating the possibility that Tax activates other pathways than these two.In addition, we showed that Tax can induce cell cycle progression in resting human T-cells using a Tax-expessing recombinant adenovirus and an IL-2 dependent human T-cell line Kit 225. The ability of Tax mutants to induce cell cycle progression paralleled those to activate the NF-κB transcription pathway, indicating that the NF-κB pathway is important for Tax-mediated cell cycle progression. However, overexpression of NF-κB did not induce cell cycle progression. These results indicate that Tax can activate other pathway (s) than typical NF-κB.