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/microliters), 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 dimer 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.
Copeland
K F
KF
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
McKay
P J
PJ
Rosenthal
K L
KL
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D006678:HIV / Q000235:genetics / Q000276:immunology; D016325:HIV Long Terminal Repeat / Q000235:genetics* / Q000276:immunology; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D014158:Transcription, Genetic