Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis

J Immunol. 2011 Mar 15;186(6):3642-52. doi: 10.4049/jimmunol.1003292. Epub 2011 Feb 11.

Abstract

Acute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. In this article, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10(+)CD8 and IL-10(-)CD8 T cells interconvert during acute disease, possibly based on recent Ag exposure. Strikingly, IL-10(+)CD8 T cells were more highly activated and cytolytic than IL-10(-)CD8 T cells, expressing greater levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Even though these cells are highly proinflammatory, IL-10 expressed by these cells was functional. Furthermore, IL-10 produced by CD8 T cells diminished disease severity in mice with coronavirus-induced acute encephalitis, suggesting a self-regulatory mechanism that minimizes immunopathological changes.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Line, Tumor
  • Cells, Cultured
  • Coronaviridae Infections / immunology
  • Coronaviridae Infections / metabolism
  • Coronaviridae Infections / prevention & control
  • Cytotoxicity, Immunologic*
  • Encephalomyelitis, Acute Disseminated / immunology*
  • Encephalomyelitis, Acute Disseminated / pathology
  • Encephalomyelitis, Acute Disseminated / prevention & control
  • Inflammation Mediators / metabolism
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / deficiency
  • Interleukin-10 / physiology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Murine hepatitis virus / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / transplantation

Substances

  • IL10 protein, mouse
  • Inflammation Mediators
  • Interleukin-10

Associated data

  • GEO/GSE25846