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Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: July 1, 2013
An activated CD8+ T cell phenotype correlates with anti-HIV activity and asymptomatic clinical status
A L Landay1, C E Mackewicz, J A Levy
1Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3864.
Insights
Specific CD8+ cells expressing HLA-DR and CD28 are key to fighting human immunodeficiency virus (HIV). These cells show reduced anti-HIV function as the disease progresses, suggesting their potential as a prognostic indicator.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- CD8+ T cells play a crucial role in controlling viral infections, including human immunodeficiency virus (HIV).
- Understanding the specific subsets of CD8+ cells responsible for anti-HIV activity is essential for developing effective therapeutic strategies.
- Phenotypic markers on CD8+ cells may correlate with their functional capacity against HIV.
Purpose of the Study:
- To investigate the relationship between cell surface marker phenotype and anti-HIV function of CD8+ T cells.
- To identify specific CD8+ cell subsets associated with antiviral activity in individuals with varying stages of HIV infection.
Main Methods:
- Multiparametric flow cytometry was used to analyze cell surface markers on CD8+ cells.
- CD8+ cell subsets expressing HLA-DR and CD28 were identified and quantified.
- In vitro assays were performed to assess the antiviral activity of separated CD8+ cell subsets.
Main Results:
- Significant changes in CD8+ cell phenotype were observed, particularly in subsets expressing HLA-DR and CD28.
- High levels of CD8+ CD28+ HLA-DR+ cells correlated with strong anti-HIV responses in infected individuals.
- Anti-HIV activity resided predominantly in CD8+ cells expressing HLA-DR or CD28.
- Longitudinal studies showed a decrease in CD8+ cell anti-HIV activity with disease progression to AIDS.
Conclusions:
- The CD8+ CD28+ HLA-DR+ cell subset is primarily responsible for natural anti-HIV activity.
- Alterations in this specific CD8+ cell subset may serve as a prognostic indicator for HIV disease progression.
Abstract:
We have examined the relation of cell surface marker phenotype to the anti-human immunodeficiency virus (HIV) function of CD8+ cells from individuals at various clinical stages of HIV infection. Multiparametric flow cytometry analysis demonstrated that the most significant changes in cell surface phenotype was found within the CD8+ cell subset expressing HLA-DR and CD28. These changes in the levels of CD28 and HLA-DR expression on CD8+ cells were found to be related to antiviral activity and have clinical relevance based on three pieces of evidence: (1) strong CD8+ cell antiviral responses were associated in infected individuals with high levels of HLA-DR+ and CD28+ subsets; (2) CD8+ cell anti-HIV activity in vitro resides predominantly in the separated CD8+ cell subsets that express HLA-DR or CD28; and (3) in longitudinal studies, CD8+ cell anti-HIV activity decreased as an individual progressed from a healthy state to an AIDS condition. Taken together, the data suggest that the CD8+ cell subset identified phenotypically as a CD8+ CD28+ HLA-DR+ cell is responsible for natural anti-HIV activity. Longitudinal studies should determine if alterations in this subset can be used as a prognostic indicator for disease progression.
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