SUPPRESSION OF ACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS LONG TERMINAL REPEAT BY CD8(+) T-CELLS IS NOT LENTIVIRUS SPECIFIC

CD8(+) T lymphocytes of HIV-1-infected individuals can efficiently suppress HIV-1 replication in CD4(+) T lymphocytes. To elucidate the molecular events underlying this suppression, we have used the HIV-1 LTR directing the chloramphenicol acetyltransferase gene (CAT) in transient transfection assays using human Jurkat T cells. In addition to supernatants of patient CD8(+) T lymphocytes (CD4(+) > 350/mu l), supernatant of a T cell clone derived by Herpesvirus saimiri (HVS)-mediated transformation of CD8(+) T lymphocytes of a patient demonstrating inhibition of virus replication were examined. Similar levels of inhibition of LTR-mediated gene expression in response to Tat or mitogenic activation with phorbol ester and calcium ionophore were observed by supernatants of both sources. The inhibitory effect of CD8(+) T lymphocytes was not exclusive to lentiviral LTRs since transcription of both the HTLV-I LTR and RSV LTR in response to mitogen was effectively inhibited. In examination of the influence of CD8(+) T cell-derived supernatant on NF kappa B-mediated activation, a diner of the HIV-1 NF kappa B elements directing CAT was markedly inhibited by supernatants of both patient CD8(+) lymphocytes and the HVS-derived CD8(+) clone. Thus the inhibitory nature of CD8(+) T lymphocytes appears not to be specific to lentiviral promoters and may mediate an inhibitory effect via the NF kappa B element.