CD8 + T Lymphocyte-Mediated Inhibition of HIV-1 Long Terminal Repeat Transcription: A Novel Antiviral Mechanism

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 HTV-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. This suppressive effect of CD8⁺ T lymphocytes on HIV-1 promoter activity could play a role in the regulation of HIV-1 replication during the asymptomatic period of HIV-1 infection.