title: L.E.A.P.S. heteroconjugate is able to prevent and treat experimental autoimmune myocarditis by altering trafficking of autoaggressive cells to the heart.
abstract: We evaluated the efficacy of the Ligand Epitope Antigen Presentation System (L.E.A.P.S.trade mark) 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 MyHCalpha(334-352) (My-1) and J peptide, derived from the sequence of human beta-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-1alpha and IP-10 in hearts. We propose that J-My-1 treatment interferes with trafficking of autoaggressive immune cells to the heart.
authors.affiliation: Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. dcihako1@jhmi.edu <dcihako1@jhmi.edu>
authors.forename: Daniela
authors.initials: D
authors.lastname: Cihakova
authors.forename: Jobert G
authors.initials: JG
authors.lastname: Barin
authors.forename: G Christian
authors.initials: GC
authors.lastname: Baldeviano
authors.forename: Miho
authors.initials: M
authors.lastname: Kimura
authors.forename: Monica V
authors.initials: MV
authors.lastname: Talor
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Zimmerman
authors.forename: Eyal
authors.initials: E
authors.lastname: Talor
authors.forename: Noel R
authors.initials: NR
authors.lastname: Rose
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D054405:Chemokine CCL3 / Q000096:biosynthesis; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis; D017635:Clonal Anergy / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000187:drug effects*; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D007144:Immunoglobulin J-Chains / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D008805:Mice, Inbred A; D009205:Myocarditis / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects
chemical_list: D054405:Chemokine CCL3; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines; D000939:Epitopes; D007144:Immunoglobulin J-Chains; D008024:Ligands