Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time

PLoS One. 2008 Jul 23;3(7):e2745. doi: 10.1371/journal.pone.0002745.


Background: T-cell immunity is thought to play an important role in controlling HIV infection, and is a main target for HIV vaccine development. HIV-specific central memory CD8(+) and CD4(+) T cells producing IFNgamma and IL-2 have been associated with control of viremia and are therefore hypothesized to be truly protective and determine subsequent clinical outcome. However, the cause-effect relationship between HIV-specific cellular immunity and disease progression is unknown. We investigated in a large prospective cohort study involving 96 individuals of the Amsterdam Cohort Studies with a known date of seroconversion whether the presence of cytokine-producing HIV-specific CD8(+) T cells early in infection was associated with AIDS-free survival time.

Methods and findings: The number and percentage of IFNgamma and IL-2 producing CD8(+) T cells was measured after in vitro stimulation with an overlapping Gag-peptide pool in T cells sampled approximately one year after seroconversion. Kaplan-Meier survival analysis and Cox proportional hazard models showed that frequencies of cytokine-producing Gag-specific CD8(+) T cells (IFNgamma, IL-2 or both) shortly after seroconversion were neither associated with time to AIDS nor with the rate of CD4(+) T-cell decline.

Conclusions: These data show that high numbers of functional HIV-specific CD8(+) T cells can be found early in HIV infection, irrespective of subsequent clinical outcome. The fact that both progressors and long-term non-progressors have abundant T cell immunity of the specificity associated with low viral load shortly after seroconversion suggests that the more rapid loss of T cell immunity observed in progressors may be a consequence rather than a cause of disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / blood
  • Acquired Immunodeficiency Syndrome / diagnosis
  • Acquired Immunodeficiency Syndrome / virology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / virology*
  • Cohort Studies
  • Cytokines / metabolism
  • Disease Progression
  • Disease-Free Survival
  • HIV Infections / blood*
  • HIV Infections / diagnosis
  • HIV Infections / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Peptides / chemistry
  • Prospective Studies
  • T-Lymphocytes / immunology
  • Time Factors
  • Treatment Outcome


  • Cytokines
  • Interleukin-2
  • Peptides
  • Interferon-gamma