Antiretroviral therapy-induced dominant interleukin-2 HIV-1 Gag CD4+ T cell response: evidence of functional recovery of HIV-1-specific CD4+ T cells

Scand J Immunol. 2011 Mar;73(3):256-65. doi: 10.1111/j.1365-3083.2010.02502.x.

Abstract

Prolonged antiretroviral treatment (ART) significantly changes the cytokine secretion capacities of HIV-1-specific T cells. However, it is unclear whether these changes result from decreased viremia or they correspond to true functional recovery of viral-specific immune response. To study this issue, we analysed the quantitative and qualitative differences of HIV-1-specific and polyclonal CD4+ and CD8+ T cells between 26 naive and 52 treated individuals. HIV-1 Gag and staphylococcal enterotoxin B (SEB)-reactive T cells were determined by flowcytometric intracellular secretion of IFN-γ or/and ΙL-2. ART resulted in increase of single IL-2 and decrease of single IFN-γ-secreting HIV-1 CD4+ T cells, while both cytokines secreting HIV-1 CD4+ T cells were presented in comparable frequencies in both groups. Viral loads correlated negatively with single IL-2 and positively with single IFN-γ-secreting HIV-1 CD4+ cells. Single IL-2 HIV-1 CD4+ T cells correlated positively with both cytokines secreting polyclonal CD8+ T cells. By qualitative analysis, a dominant IL-2 HIV-1 CD4+ T cell response (> 70% single IL-2) was identified only in ART suppressed patients, who also generated increased dual specific polyclonal CD8+ T cells. Polyfunctional HIV-1 CD4+ T cell responses were detected even in naive individuals with high viremia. In conclusion, the presence of dominant IL-2 HIV-1 CD4+ T cell response, associated with increased CD8+ T cells capable to produce IL-2, indicates that the recovery of HIV-1-specific CD4+ T cell functionality under ART is a feasible goal. Furthermore, polyfunctional HIV-1 CD4+ T cell responses seem not to be directly involved in viral replication control.

MeSH terms

  • Adult
  • Aged
  • Anti-Retroviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cell Separation
  • Female
  • Flow Cytometry
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology
  • Humans
  • Interleukin-2 / immunology
  • Male
  • Middle Aged
  • gag Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • Anti-Retroviral Agents
  • Interleukin-2
  • gag Gene Products, Human Immunodeficiency Virus