HIV controllers are distinguished by chemokine expression profile and HIV-specific T-cell proliferative potential

J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):427-37. doi: 10.1097/QAI.0b013e3182454fcd.


Background: HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers.

Methods: Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses.

Results: HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control.

Conclusions: Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation*
  • Cytokines / metabolism*
  • Female
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV-1 / physiology*
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Virus Replication / immunology


  • Cytokines