IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells

Blood. 2009 Jul 9;114(2):346-56. doi: 10.1182/blood-2008-12-191296. Epub 2009 Apr 13.


Murine models indicate that interleukin-10 (IL-10) can suppress viral clearance, and interventional blockade of IL-10 activity has been proposed to enhance immunity in chronic viral infections. Increased IL-10 levels have been observed during HIV infection and IL-10 blockade has been shown to enhance T-cell function in some HIV-infected subjects. However, the categories of individuals in whom the IL-10 pathway is up-regulated are poorly defined, and the cellular sources of IL-10 in these subjects remain to be determined. Here we report that blockade of the IL-10 pathway augmented in vitro proliferative capacity of HIV-specific CD4 and CD8 T cells in individuals with ongoing viral replication. IL-10 blockade also increased cytokine secretion by HIV-specific CD4 T cells. Spontaneous IL-10 expression, measured as either plasma IL-10 protein or IL-10 mRNA in peripheral blood mononuclear cells (PBMCs), correlated positively with viral load and diminished after successful antiretroviral therapy. IL-10 mRNA levels were up-regulated in multiple PBMC subsets in HIV-infected subjects compared with HIV-negative controls, particularly in T, B, and natural killer (NK) cells, whereas monocytes were a major source of IL-10 mRNA in HIV-infected and -uninfected individuals. These data indicate that multiple cell types contribute to IL-10-mediated immune suppression in the presence of uncontrolled HIV viremia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Cells, Cultured
  • Disease
  • Gene Expression Regulation
  • HIV Infections / complications
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • RNA, Messenger / genetics
  • Receptors, Interleukin-10 / immunology
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Up-Regulation / immunology*
  • Viremia / complications
  • Viremia / genetics
  • Viremia / immunology*
  • Viremia / metabolism


  • RNA, Messenger
  • Receptors, Interleukin-10
  • Interleukin-10