Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells.
Dysregulation of cytokines secreted by T cells may play an important role in the pathogenesis of AIDS. To investigate the effects of human immunodeficiency virus type 1 (HIV-1) Tat on interleukin-2 (IL-2) expression, we used IL-2 promoter-chloramphenicol acetyltransferase constructs and IL-2-secreting Jurkat T cells as a model system. Transient expression of HIV-1 Tat induced a five- to eightfold increase in IL-2 promoter activity in Jurkat T cells stimulated with phytohemagglutinin and phorbol myristate acetate. IL-2 secretion was increased more than twofold in both Jurkat T cells and primary T cells stimulated by extracellular HIV-1 Tat protein. Analysis of mRNA suggested that Tat exerts its effect on IL-2 primarily at the transcriptional level. The NF-kappa B site at positions -206 to -195 of the IL-2 promoter was required but not sufficient for the Tat effect. The Tat-mediated increase in IL-2 promoter activity could selectively be blocked by antisense tat or-unlike the analogous effect of human T-cell lymphotropic virus type 1 Tax-by cyclosporin A. The observed increase in IL-2 levels might facilitate virus spread from or to T cells. Furthermore, it might contribute to the hypergammaglobulinemia or, together with other cytokines found to be dysregulated, the T-helper cell dysfunctions observed in AIDS patients.
Westendorp
M O
MO
Division of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg.
Li-Weber
M
M
Frank
R W
RW
Krammer
P H
PH
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015696:Gene Products, tat / Q000276:immunology*; D016355:Genes, pX; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D054322:tat Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D015696:Gene Products, tat; D007376:Interleukin-2; D016328:NF-kappa B; D054322:tat Gene Products, Human Immunodeficiency Virus