L.E.A.P.S. heteroconjugate is able to prevent and treat experimental autoimmune myocarditis by altering trafficking of autoaggressive cells to the heart.
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.
Cihakova
Daniela
D
Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. dcihako1@jhmi.edu <dcihako1@jhmi.edu>
Barin
Jobert G
JG
Baldeviano
G Christian
GC
Kimura
Miho
M
Talor
Monica V
MV
Zimmerman
Daniel H
DH
Talor
Eyal
E
Rose
Noel R
NR
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
D054405:Chemokine CCL3; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines; D000939:Epitopes; D007144:Immunoglobulin J-Chains; D008024:Ligands