Differential induction of IgE-mediated anaphylaxis after soluble vs. cell-bound tolerogenic peptide therapy of autoimmune encephalomyelitis

Cassandra E. Smith, Todd N. Eagar, Jack L. Strominger, Stephen D. Miller

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

The ability of different forms of myelin peptides to induce tolerance for the treatment of preestablished murine experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, was evaluated. i.v. administration of myelin peptide-pulsed, ethylene carbodiimide-fixed syngeneic splenocytes, but not soluble myelin peptide monomers or oligomers, proved exceedingly effective at treating preestablished EAE, resulting in amelioration of disease progression. In addition to the lack of therapeutic efficacy of soluble peptide and peptide oligomer, administering them i.v. after the onset of clinical symptoms in many but not all peptide-induced EAE models led to a rapid-onset anaphylactic reaction characterized by respiratory distress, erythema, decreased body temperature, unresponsiveness, and, often, death. By using anti-IgE antibody treatments and mice with targeted mutations of the FcγRIII α-chain or the common γ-chain of FcεRI and FcγRI/III, we demonstrate that IgE crosslinking of FcεRI appears to be necessary and sufficient for myelin peptide-induced anaphylaxis. The implications of these findings to myelin peptide/protein tolerance strategies for the treatment of multiple sclerosis are discussed.

Original languageEnglish (US)
Pages (from-to)9595-9600
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number27
DOIs
StatePublished - Jul 5 2005

Keywords

  • Myelin
  • Tolerance

ASJC Scopus subject areas

  • General

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