Activation of the GM-CSF promoter by HTLV-I and -II tax proteins

Abstract

Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by normal T lymphocytes requires activation by antigen, mitogen or lectin, whereas T-cell lines transformed by human T-cell leukemia virus type I (HTLV-I) or type II (HTLV-II) constitutively produce high levels of GM-CSF. Using transient cotransfection assays, we demonstrate that introduction of the tax gene of either HTLV-I or HTLV-II is sufficient to activate GM-CSF promoter constructs in an unstimulated T-cell line. The GM-CSF 5' flanking sequences previously shown to be sufficient for GM-CSF induction following T-cell activation are also sufficient for activation by the HTLV tax proteins. The sequences required for trans-activation of GM-CSF are distinct from those required for the activation of other T-cell-inducible genes (IL-2R alpha, IL-2) by tax, suggesting that tax can have pleiotropic effects on gene expression in T cells. Constitutive GM-CSF production by HTLV-infected T cells may therefore be due to trans-activation of its promoter by tax. Expression of GM-CSF by HTLV-I infected lymphocytes may be important in the granulocytosis and eosinophilia frequently seen in patients with HTLV-I-induced adult T-cell leukemia/lymphoma.