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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
HIV-specific CD8+ T cells from elite controllers are primed for survival
Jiyu Yan1, Steffanie Sabbaj, Anju Bansal
1Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Journal of Virology
|March 2, 2013
Summary
Elite controllers resist HIV-specific T cell death better than treated patients, suggesting survival factor upregulation. This apoptosis resistance is partially reversible with antiretroviral therapy (ART), offering insights for HIV-1 vaccines.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- HIV-specific cytotoxic T lymphocytes (CTL) are prone to apoptosis, a potential viral escape mechanism.
- Elite controllers (EC) control HIV without antiretroviral therapy (ART), suggesting enhanced T cell survival.
- Understanding T cell apoptosis in HIV is crucial for vaccine development and predicting treatment responses.
Purpose of the Study:
- To investigate whether elite controllers (EC) upregulate survival factors to resist apoptosis in HIV-specific CD8 T cells.
- To compare apoptosis markers in HIV-specific CTL from EC, successfully treated (ST) patients, and chronically infected individuals starting ART.
- To determine if the pro-apoptotic phenotype in HIV-specific T cells is reversible with ART.
Main Methods:
- Cross-sectional and longitudinal analysis of proapoptotic (cleaved caspase-3) and antiapoptotic (Bcl-2) markers.
- Assessment of cytomegalovirus (CMV) and HIV-specific CD8 T cells in HIV-infected subjects with varying viral control.
- Comparison of T cell apoptosis markers between EC, ST patients, and individuals initiating ART.
Main Results:
- HIV-specific CTL from EC exhibited greater resistance to apoptosis compared to ST patients.
- Initiating ART in chronically infected individuals decreased the frequency of death-prone HIV-specific T cells.
- The observed decrease in T cell apoptosis with ART was significant but did not reach the levels seen in EC.
Conclusions:
- HIV-specific CTL from EC possess enhanced apoptosis resistance, likely due to upregulated survival factors.
- Antiretroviral therapy can partially reverse the pro-apoptotic phenotype of HIV-specific T cells.
- Identifying apoptotic factors in EC is key for developing effective HIV-1 vaccines and predicting immune responses.
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