ABERRANT REGULATION OF CYTOKINES IN HIV-1 TAT(72)-TRANSGENIC MICE

The trans-activator of transcription or TAT gene from HIV-1 encodes a protein that increases the processivity of transcription from the HIV- 1 genome. TAT protein can also affect cellular processes in the absenc e of its ribonucleic HIV target sequence trans activation response ele ment and may be responsible for some aspects of HIV pathogenesis apart from infectious virus or other viral gene products. We have previousl y shown that TAT(72) decreases CTL activity in TAT(72)-transgenic mice , and we now demonstrate aberrant regulation of mitogen-elicited IL-2 at both transcriptional and translational levels. In contrast, alloant igen stimulation resulted in increased IL-6 and IL-10 production in th e TAT(72)-transgenic mice. Con A-stimulated cultures of splenic lympho cytes from TAT(72)-transgenic mice do not undergo clonal proliferation of CD4(+) cells as compared with CD8(+) cells monitored over 72 h. Th ese results suggest that TAT is sufficient to induce some pathology as sociated with AIDS and is a potent immunologic manipulator apart from its function as trans-activator.