Antigen-specific CD8+ T cells mediate a peptide-induced fatal syndrome

Aaron J. Johnson, Yanice Mendez-Fernandez, Ann M. Moyer, Cari R. Sloma, Istvan Pirko, Matthew S. Block, Moses Rodriguez, Larry R. Pease

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Peptide immunotherapy both activates and suppresses the T cell response against known pepiide Ags. Although pretreatment with VP2121-130 peptide inhibits the development of antiviral CTL specific for the immunodominant Db:VP2121-130 epitope expressed during acute Theiler's murine encephalomyelitis virus infection, i.v. injection of this same peptide or MHC tetramers containing the peptide during an ongoing antiviral CTL response results in a peptide-induced fatal syndrome (PIFS) within 48 h. Susceptibility to PIFS is dependent on peptide-speciflc CD8+ T cells, varies among inbred strains of mice, and is not mediated by traditionally defined mechanisms of shock. Analyses using bone marrow chimeras and matant mice demonstrate that susceptibility to PIFS is determined by the genotype of bone marrow-derived cells and requires the expression of perform. Animals responding to peptide treatment with PIFS develop classical stress responses in the brain. These findings raise important considerations for the development of peptide therapies for active diseases to modify immune responses involving expanded populations of T cells. In summary, treatment with pep tides or MHC-tetramers during a peptide-specific immune response can result in a fatal shock-like syndrome. Susceptibility to the syndrome is genetically determined, is mediated by CD8+ T cells, and requires expression of perforin. These findings raise concerns about the use of peptides and MHC tetramers in therapeutic schemes.

Original languageEnglish (US)
Pages (from-to)6854-6862
Number of pages9
JournalJournal of Immunology
Volume174
Issue number11
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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