title: CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: a novel antiviral mechanism.
abstract: HIV-1 infection evokes a vigorous antiviral response that may participate in resolving the initial peak of plasma viremia and maintenance of the asymptomatic state. CD8+ T lymphocytes of HIV-1-infected individuals play a critical role in the cellular anti-HIV response. In agreement with previous reports, we observed a potent suppressive effect on HIV-1 production from autologous CD4+ T lymphocytes by CD8+ T lymphocytes from asymptomatic HIV-1-infected individuals. To elucidate the mechanism(s) of the nonlytic suppressive antiviral activity, we examined the effect of CD8+ T lymphocytes on the transcriptional activity of the HIV-1 promoter (HIV-LTR). CD8+ lymphocytes from HIV-1-infected asymptomatic individuals suppressed tat-mediated HIV-LTR transcription in CD4+ lymphocytes. HIV-LTR transcriptional activity was suppressed by CD8 lymphocytes to an extent similar to tat-mediated transcription whereas CMV immediate early gene promoter activity was not affected. In contrast to the suppressive effect seen with CD8+ lymphocytes from HIV-1-infected individuals, CD8+ lymphocytes from uninfected individuals did not significantly inhibit tat-mediated or HIV-LTR transcription. The transcriptional inhibitory activity was not MHC class I restricted and could be mediated by a soluble factor(s). Supernatants from some CD8+ T lymphocyte cultures from HIV-1+ individuals exerted an inhibitory effect on tat-mediated HIV-LTR transcription comparable to that seen with CD8+ cells. In conclusion, CD8+ lymphocytes from asymptomatic HIV-1+ individuals could suppress virus production by inhibiting HIV-1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: K J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: J A
authors.initials: JA
authors.lastname: Bartlett
authors.forename: D P
authors.initials: DP
authors.lastname: Bolognesi
authors.forename: M L
authors.initials: ML
authors.lastname: Greenberg
mesh_terms: D016827:CD8 Antigens; D002478:Cells, Cultured; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D015395:Histocompatibility Antigens Class I; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I