Heat shock proteins and experimental autoimmune encephalomyelitis II: Environmental infection and extra-neuraxial inflammation alter the course of chronic relapsing encephalomyelitis

Gary Birnbaum*, Linda Kotilinek, Stephen D. Miller, Cedric S. Raine, Yan Ling Gao, Paul V. Lehmann, Radhey S. Gupta

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

We wished to study how infections might trigger relapses of autoimmune diseases such as multiple sclerosis (MS) and encephalomyelitis (EAE). We hypothesized that immune responses to heat shock proteins (hsp) induced by an infection could modulate responses to autoantigens. We induced extra- neuraxial inflammation in SJL mice housed either in specific-pathogen free (SPF) or conventional facilities. Mice in conventional housing are continuously exposed to large numbers of infectious agents. Spleen cell proliferative responses to human HSP60 and bacterial HSP65 were measured as were numbers of cells secreting IFN-γ or IL-5. Proliferative responses to HSP60 were increased in conventionally housed mice compared to SPF mice and this was associated with skewing of secreted cytokines toward a Th2 pattern. Skewing toward a Th1 pattern was noted in SPF mice. Acute and relapsing EAE was induced in both groups of mice. Acute EAE was, in general, equivalent in all groups. However, SPF mice had more severe relapses than did conventionally housed animals and these differences were amplified by extra- neuraxial inflammation. Immunocytochemical analyses of brains from mice with relapsing EAE showed that increased numbers of brain γ/δ cells were associated with disease remission. Our data suggest that frequent exposure to infectious agents leads to a relative Th2 skewing of immune responses to hsp and that this is associated with milder, less frequent relapses of EAE. They also support the concept that immune responses to hsp are of potential importance in exacerbating and perpetuating organ-restricted autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)149-161
Number of pages13
JournalJournal of Neuroimmunology
Volume90
Issue number2
DOIs
StatePublished - Oct 1 1998

Keywords

  • Encephalomyelitis
  • Heat shock proteins
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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