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HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells
Michael R Betts1, Martha C Nason, Sadie M West
1Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Blood
|February 10, 2006
Summary
The quality, not quantity, of CD8(+) T-cell immune responses correlates with HIV disease progression. Highly functional CD8(+) T cells in nonprogressors are key to controlling viral load, unlike in progressors.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Developing an HIV vaccine requires identifying a reliable immune correlate of protection.
- Previous studies found no conclusive link between HIV-specific CD8(+) T-cell quantity/breadth and protection.
Purpose of the Study:
- To assess the quality of HIV-specific CD8(+) T-cell responses by measuring multiple immune functions.
- To determine if T-cell quality correlates with HIV disease progression or viral load.
Main Methods:
- Simultaneously measured 5 CD8(+) T-cell functions (degranulation, IFN-gamma, MIP-1beta, TNF-alpha, IL-2).
- Compared functional profiles in chronically HIV-infected individuals (progressors) and elite nonprogressors.
- Assessed correlation with HLA type, T-cell memory phenotype, and viral load.
Main Results:
- HIV progressors showed limited CD8(+) T-cell functionality compared to nonprogressors.
- Limited functionality was HIV-specific, independent of HLA type and memory phenotype, and unaffected by treatment.
- Higher functionality of CD8(+) T cells inversely correlated with viral load in progressors.
Conclusions:
- CD8(+) T-cell functional quality, not quantity or phenotype, is a crucial immune correlate of HIV disease progression.
- High-quality CD8(+) T-cell responses may be a key factor for evaluating HIV vaccine efficacy.