Dynamics and consequences of IL-21 production in HIV-infected individuals: a longitudinal and cross-sectional study

J Immunol. 2010 Jan 1;184(1):114-26. doi: 10.4049/jimmunol.0901967. Epub 2009 Nov 30.


IL-21 is a relatively newly discovered immune-enhancing cytokine that plays an essential role in controlling chronic viral infections. It is produced mainly by CD4(+) T cells, which are also the main targets of HIV-1 and are often depleted in HIV-infected individuals. Therefore, we sought to determine the dynamics of IL-21 production and its potential consequences for the survival of CD4(+) T cells and frequencies of HIV-specific CTL. For this purpose, we conducted a series of cross-sectional and longitudinal studies on different groups of HIV-infected patients and show in this study that the cytokine production is compromised early in the course of the infection. The serum cytokine concentrations correlate with CD4(+) T cell counts in the infected persons. Among different groups of HIV-infected individuals, only elite controllers maintain normal production of the cytokine. Highly active antiretroviral therapy only partially restores the production of this cytokine. Interestingly, HIV infection of human CD4(+) T cells inhibits cytokine production by decreasing the expression of c-Maf in virus-infected cells, not in uninfected bystander cells. We also show that the frequencies of IL-21-producing HIV-specific, but not human CMV-specific, Ag-experienced CD4(+) T cells are decreased in HIV-infected viremic patients. Furthermore, we demonstrate in this study that recombinant human IL-21 prevents enhanced spontaneous ex vivo death of CD4(+) T cells from HIV-infected patients. Together, our results suggest that serum IL-21 concentrations may serve as a useful biomarker for monitoring HIV disease progression and the cytokine may be considered for immunotherapy in HIV-infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antiretroviral Therapy, Highly Active
  • Biomarkers / analysis*
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Carrier Proteins / biosynthesis
  • Cross-Sectional Studies
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • Humans
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Longitudinal Studies
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection


  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • CMIP protein, human
  • Carrier Proteins
  • Interleukins
  • RNA, Small Interfering
  • interleukin-21