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

Blood. 2006 Jun 15;107(12):4781-9. doi: 10.1182/blood-2005-12-4818. Epub 2006 Feb 7.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 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


  • AIDS Vaccines
  • Cytokines
  • HLA Antigens