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Suppression of HIV replication by CD8+ cell clones derived from HIV-infected and uninfected individuals
F W Hsueh1, C M Walker, D J Blackbourn
1Department of Medicine, University of California, School of Medicine, San Francisco 94143.
Insights
Certain CD8+ T-cell clones can suppress human immunodeficiency virus (HIV) replication without killing cells. This antiviral activity is linked to a secreted factor, offering potential therapeutic strategies for HIV infection.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus (HIV) infection remains a global health challenge.
- CD8+ T-cells play a crucial role in controlling viral infections.
- Understanding mechanisms of HIV suppression by immune cells is vital for therapeutic development.
Purpose of the Study:
- To investigate the antiviral properties of CD8+ T-cell clones derived from HIV-infected and uninfected individuals.
- To identify the mechanisms by which CD8+ T-cells suppress HIV replication.
- To explore the potential of CD8+ T-cell clones as a therapeutic strategy for HIV.
Main Methods:
- Isolation and cloning of CD8+ T-cells from peripheral blood mononuclear cells (PBMCs) of HIV-infected and uninfected donors.
- Co-culture assays involving CD8+ T-cell clones and HIV-infected CD4+ T-cells (laboratory-generated or from patients).
- Measurement of HIV replication suppression and analysis of secreted factors.
Main Results:
- Several CD8+ T-cell clones demonstrated the ability to suppress HIV replication in co-culture experiments.
- Suppression of viral production occurred without significant cytotoxicity to the target CD4+ cells.
- The antiviral activity of these CD8+ clones correlated with the production of a filterable, biologically active factor.
Conclusions:
- CD8+ T-cell clones possess potent, non-cytotoxic antiviral activity against HIV.
- A secreted factor produced by these CD8+ T-cell clones mediates HIV suppression.
- These findings highlight the potential of CD8+ T-cell clones and their secreted factors for novel HIV therapeutics, including adoptive cell transfer.
Abstract:
CD8+ cell clones have been derived from peripheral blood mononuclear cells of human immunodeficiency virus (HIV)-infected and uninfected individuals. Several of these cloned cells have the ability to suppress HIV replication when cocultured with CD4+ cells acutely infected in the laboratory with HIV or with infected CD4+ cells from infected subjects. Suppression of virus production occurs without killing the target cells. With the CD8+ cell clones studied, this antiviral response correlated with production of a filterable factor that has antiviral activity. These cell clones offer the opportunity for identification of the factor mediating suppression of HIV replication. Moreover, adoptive transfer of cell clones might provide a valuable therapeutic approach for HIV-infected individuals.