Persistent loss of IL-27 responsiveness in CD8+ memory T cells abrogates IL-10 expression in a recall response

Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18535-40. doi: 10.1073/pnas.1119133109. Epub 2012 Oct 22.


CD8+ T cells are central to the eradication of intracellular pathogens, but they can also act to limit inflammation and immunopathology. During primary respiratory viral infection CD8+ effector T cells release the immunosuppressive cytokine IL-10, which is essential for host survival. Here we report that CD8+ T-cell-derived IL-10 is absent in a recall response. We show in mice that the lack of IL-10 is due to a persistent loss of IL-27 responsiveness in CD8+ memory T cells, caused by down-regulation of the common cytokine receptor, glycoprotein 130. CD8+ memory T cells secreted less IL-10 when activated in the presence of IL-27 than did naïve controls, and retroviral expression of glycoprotein 130 restored IL-10 and reduced IFN-γ production upon restimulation. We demonstrate that human CD8+ memory cells are also characterized by impaired IL-27 responsiveness. Our data suggest that CD8+ T-cell activation involves a persistent loss of specific cytokine receptors that determines the functional potential of these cells during rechallenge infection.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytokine Receptor gp130 / metabolism
  • Down-Regulation / drug effects
  • Humans
  • Immunologic Memory / drug effects*
  • Interleukin-10 / immunology*
  • Interleukin-17 / pharmacology*
  • Lung / drug effects
  • Lung / immunology
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / pathology
  • Respiratory Tract Infections / virology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology


  • Interleukin-17
  • Interleukin-10
  • Cytokine Receptor gp130