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CD8+ T cells from HIV type 1-seronegative individuals suppress virus replication in acutely infected cells
B Røsok1, P Voltersvik, B M Larsson
1Department of Microbiology and Immunology, Gade Institute, University of Bergen, Norway.
Insights
CD8+ lymphocytes (CD8 cells) from HIV-negative individuals can suppress human immunodeficiency virus (HIV) replication in CD4+ lymphocytes (CD4 cells). This antiviral activity is present even without prior HIV exposure, demonstrating a key innate immune response.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- CD8+ lymphocytes (CD8 cells) inhibit human immunodeficiency virus (HIV) replication in vitro.
- This effect was previously observed only with CD8 cells from HIV-seropositive individuals.
Purpose of the Study:
- To investigate if CD8 cells from HIV-negative individuals can suppress HIV replication in experimentally infected CD4+ lymphocytes (CD4 cells).
Main Methods:
- CD4 cells were infected with primary HIV-1 and HIV-2 isolates.
- Graded numbers of CD8 cells from HIV-negative donors were added to infected cultures.
- HIV replication was quantified by measuring HIV p24 levels.
Main Results:
- CD8 cells from HIV-negative donors suppressed HIV-1 and HIV-2 replication in autologous CD4 cells.
- This antiviral activity was reproducible and comparable to that of CD8 cells from HIV-positive individuals.
- Suppression varied based on HIV viral dose and phenotype; infected cells were not eliminated.
Conclusions:
- In vivo HIV exposure is not required for CD8 cells to suppress HIV replication.
- CD8 cells from HIV-naive individuals possess innate antiviral capabilities against HIV.
- This finding has implications for understanding natural HIV control mechanisms.
Abstract:
CD8+ lymphocytes (CD8 cells) have been shown to inhibit replication of the human immunodeficiency virus (HIV) in vitro when cocultured with HIV-infected CD4+ lymphocytes (CD4 cells). This suppressive effect on HIV replication in experimentally infected CD4 cells has so far been demonstrated only for CD8 cells from HIV-seropositive individuals. In the present study we have investigated if CD8 cells from HIV-negative individuals can also suppress HIV replication in experimentally infected CD4 cells. Positively selected CD4 cells were infected with phenotypically different primary isolates of HIV type 1 and 2 (HIV-1 and HIV-2). Graded numbers of CD8 cells were added to the infected cultures. The T cells were activated by antibodies directed against the CD3 molecule or the T cell receptor. Culture supernatants were harvested for HIV p24 quantitation and the CD8 suppression of HIV replication was calculated by comparing p24 levels from parallel cultures in the presence or absence of CD8 cells from different donors. We show that CD8 cells from unexposed HIV-seronegative blood donors are able to control HIV-1 and HIV-2 replication in experimentally infected autologous CD4 cells. The antiviral activity of CD8 cells from and HIV-naive individual was reproducible over time and the suppressive effect was comparable to that seen with CD8 cells from HIV-positive individuals. The infected cells were not eliminated from the cultures. The suppressive effect of CD8 cells varied depending on the dose and biological phenotype of the virus used for infection. Thus, exposure to HIV in vivo is not a prerequisite for CD8 cells to exert a suppressive effect on HIV replication in acutely infected cells.