Suppression of Activation of the Human Immunodeficiency Virus Long Terminal Repeat by CD8 + T Cells Is Not Lentivirus Specific

Abstract

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/μl), 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 NFκB-mediated activation, a dimer of the HIV-1 NFκB 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 NFκB element.