L.E.A.P.S. heteroconjugate is able to prevent and treat experimental autoimmune myocarditis by altering trafficking of autoaggressive cells to the heart

Daniela Cihakova, Jobert G. Barin, G. Christian Baldeviano, Miho Kimura, Monica V. Talor, Daniel H. Zimmerman, Eyal Talor, Noel R. Rose

Research output: Contribution to journalArticlepeer-review

Abstract

We evaluated the efficacy of the Ligand Epitope Antigen Presentation System (L.E.A.P.S.™) in preventing or treating experimental autoimmune myocarditis (EAM) in A/J mice. L.E.A.P.S. (here, J-My-1) is a conjugate of the myocarditogenic peptide of cardiac myosin MyHCα334-352 (My-1) and J peptide, derived from the sequence of human β-2 microglobulin. Remarkably, early prophylactic (J-My-1 injected on days - 14 and - 7 before EAM induction), late prophylactic (J-My-1 injected on days 0, 7, 14, and 21), and therapeutic (J-My-1 injected on days 7, 14, and 21 or 10, 17 and 24) administration of J-My-1 significantly decreased the incidence and severity of EAM. However, extended therapeutic treatment was associated with anaphylaxis and death, corresponding with global immune activation associated with J-My-1 treatment. In J-My1-treated animals, we observed expanded numbers of activated CD69+ and CD44+ CD4+ and CD8+ T cells in the spleens. J-My-1 treatment also increased the proportion of CD11c+ dendritic cells in spleens and induced strong production of anti-J-My-1 specific antibodies. J-My-1 injections resulted in decreased levels of chemokines MIP-1α and IP-10 in hearts. We propose that J-My-1 treatment interferes with trafficking of autoaggressive immune cells to the heart.

Original languageEnglish (US)
Pages (from-to)624-633
Number of pages10
JournalInternational immunopharmacology
Volume8
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • Altered peptide ligand (APL)
  • Antigen-specific therapy
  • Autoimmunity
  • Experimental autoimmune myocarditis (EAM)
  • Myocarditis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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