Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands

Ian R Humphreys, Carl de Trez, April Kinkade, Chris A Benedict, Michael Croft, Carl F Ware

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104 Citations (Scopus)


The salivary glands represent a major site of cytomegalovirus replication and transmission to other hosts. Despite control of viral infection by strong T cell responses in visceral organs cytomegalovirus replication continues in the salivary glands of mice, suggesting that the virus exploits the mucosal microenvironment. Here, we show that T cell immunity in the salivary glands is limited by the induction of CD4 T cells expressing the regulatory cytokine interleukin (IL)-10. Blockade of IL-10 receptor (IL-10R) with an antagonist antibody dramatically reduced viral load in the salivary glands, but not in the spleen. The mucosa-specific protection afforded by IL-10R blockade was associated with an increased accumulation of CD4 T cells expressing interferon gamma, suggesting that IL-10R signaling limits effector T cell differentiation. Consistent with this, an agonist antibody targeting the tumor necrosis factor receptor superfamily member OX40 (TNFRSF4) enhanced effector T cell differentiation and increased the number of interferon gamma-producing T cells, thus limiting virus replication in the salivary glands. Collectively, the results indicate that modulating effector T cell differentiation can counteract pathogen exploitation of the mucosa, thus limiting persistent virus replication and transmission.

Original languageEnglish
Pages (from-to)1217-1225
Number of pages9
JournalThe Journal of Experimental Medicine
Issue number5
Publication statusPublished - 2007


  • Animals
  • Antibodies
  • CD4-Positive T-Lymphocytes
  • Cell Differentiation
  • DNA Primers
  • Female
  • Flow Cytometry
  • Herpesviridae Infections
  • Interferon-gamma
  • Interleukin-10
  • Mice
  • Mice, Inbred C57BL
  • Muromegalovirus
  • Receptors, Interleukin-10
  • Receptors, OX40
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salivary Glands
  • Virus Replication


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