Induction of cytokines in glial cells by trans activator of human T-cell lymphotropic virus type I.

Human T-cell lymphotropic virus type I (HTLV-I), the cause of adult T-cell leukemia, is also associated with the neurological disease, TSP/HAM (tropical spastic paraparesis/HTLV-I associated myelopathy). The HTLV-I genome encodes a protein, Tax, that trans activates viral and cellular gene transcription. To understand the mechanisms for the production of cytokines by HTLV-I in nervous tissue, we examined their expression in glial cells which carried the Tax-expressing vector. We demonstrated that Tax expression enhanced the production by glial cells of interleukin (IL)-1, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF) beta. We suggest that the excessive production of cytokines in nervous tissue may play a role in pathogenesis of TSP/HAM. Glial cells that carry the tax gene may provide a model useful for in vitro study of the mechanism of production of cytokines in the nervous system.