IRF-4 activities in HTLV-I-induced T cell leukemogenesis

We summarize recent studies on the activation and regulation of interferon (IFN) regulatory factor-4 (IRF-4) and its function in activated T cells, human T cell lymphoma virus (HTLV-I)-infected T cells, and HTLV-I-induced adult T cell leukemia (ATL). We have examined the specific mechanisms underlying the expression and regulation of the IRF-4 transcription factor in HTLV-I-infected cells and have shown that constitutive IRF-4 expression is exclusive to the transformed, leukemic ATL phenotype as opposed to the nonleukemic HTLV-I associated myelopathies/tropical spastic paraparesis (HAM/TSP) phenotype. In contrast, IRF-4 is only transiently induced in T lymphocytes activated by signals that mimic stimulation through the T cell receptor (TCR). In vivo and in vitro analyses have identified several regulatory regions within the human IRF-4 promoter that interact with the transcriptional regulators NF-kappaB, NF-AT, and Sp-1 to drive IRF-4 production in HTLV-I-infected, ATL-derived cells. cDNA array analysis of an IRF-4-expressing T cell line has also provided valuable insight into potential IRF-4 target genes. Further investigation of these novel IRF-4-regulated genes will permit a mechanistic understanding of IRF-4 function in HTLV-I-induced leukemogenesis.