HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells.

Abstract

Establishing a CD8(+) T cell-mediated immune correlate of protection in HIV disease is crucial to the development of vaccines designed to generate cell-mediated immunity. Historically, neither the quantity nor breadth of the HIV-specific CD8(+) T-cell response has correlated conclusively with protection. Here, we assess the quality of the HIV-specific CD8(+) T-cell response by measuring 5 CD8(+) T-cell functions (degranulation, IFN-gamma, MIP-1beta, TNF-alpha, and IL-2) simultaneously in chronically HIV-infected individuals and elite nonprogressors. We find that the functional profile of HIV-specific CD8(+) T cells in progressors is limited compared to that of nonprogressors, who consistently maintain highly functional CD8(+) T cells. This limited functionality is independent of HLA type and T-cell memory phenotype, is HIV-specific rather than generalized, and is not effectively restored by therapeutic intervention. Whereas the total HIV-specific CD8(+) T-cell frequency did not correlate with viral load, the frequency and proportion of the HIV-specific T-cell response with highest functionality inversely correlated with viral load in the progressors. Thus, rather than quantity or phenotype, the quality of the CD8(+) T-cell functional response serves as an immune correlate of HIV disease progression and a potential qualifying factor for evaluation of HIV vaccine efficacy.

• Authors: Michael R Betts, Martha C Nason, Sadie M West, Stephen C De Rosa, Stephen A Migueles, Jonathan Abraham, Michael M Lederman, Jose M Benito, Paul A Goepfert, Mark Connors, Mario Roederer, Richard A Koup
• Journal: Blood (Blood) Vol. 107 Issue 12 Pg. 4781-9 (Jun 15 2006) ISSN: 0006-4971 [Print] United States
• PMID: 16467198 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• AIDS Vaccines
• Cytokines
• HLA Antigens

Topics

• AIDS Vaccines (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Cytokines (immunology)
• Disease Progression
• Female
• HIV Infections (immunology)
• HLA Antigens (immunology)
• Humans
• Immunologic Memory (immunology)
• Lymphocyte Activation (immunology)
• Male
• Viral Load