IMMUNE HYPERACTIVATION OF HIV-1-INFECTED T-CELLS MEDIATED BY TAT AND THE CD28 PATHWAY

Human immunodeficiency virus-type 1 (HIV-1) infection is characterized by a chronic state of immune hyperactivation in patients. Infection o f human peripheral blood lymphocytes with HIV-1 in vitro resulted in i ncreased interleukin-2 (IL-2) secretion in response to T cell activati on via the CD3 and CD28 receptors. Expression of the HIV-1 transactiva tor Tat recapitulated this phenotype and was associated with increased IL-2 secretion in response to costimulation with CD3 plus CD28. IL-2 superinduction by Tat occurred at the transcriptional level, was media ted by the CD28-responsive element in the IL-2 promoter, and was exclu sively dependent on the 29 amino acids encoded by the second exon of T at.