title: In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis.
abstract: A number of Ag-specific approaches have been developed that ameliorate experimental allergic encephalomyelitis (EAE), an animal model for the human autoimmune disease multiple sclerosis. Translation to humans, however, remains a consideration, justifying the search for more insight into the mechanism underlying restoration of self-tolerance. Ig-proteolipid protein (PLP) 1 and Ig-myelin oligodendrocyte glycoprotein (MOG) are Ig chimeras carrying the encephalitogenic PLP 139-151 and MOG 35-55 amino acid sequence, respectively. Ig-PLP1 ameliorates EAE in SJL/J (H-2(s)) mice while Ig-MOG modulates the disease in C57BL/6 (H-2(b)) animals. In this study, we asked whether the chimeras would suppress EAE in F(1) mice expressing both parental MHC alleles and representing a polymorphism with more relevance to human circumstances. The results show that Ig-MOG modulates both PLP1 and MOG peptide-induced EAE in the F(1) mice, whereas Ig-PLP1 counters PLP1 EAE but exacerbates MOG-induced disease. This in trans aggravation of MOG EAE by Ig-PLP1 operates through induction of PLP1-specific T cells producing IL-5 that sustained inhibition of MOG-specific Abs leading to exacerbation of EAE. Thus, in trans T cell tolerance, which should be operative in polymorphic systems, can aggravate rather than ameliorate autoimmunity. This phenomenon possibly takes place through interference with protective humoral immunity.
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA.
authors.forename: J Jeremiah
authors.initials: JJ
authors.lastname: Bell
authors.forename: Rohit D
authors.initials: RD
authors.lastname: Divekar
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ellis
authors.forename: Jason A
authors.initials: JA
authors.lastname: Cascio
authors.forename: Cara L
authors.initials: CL
authors.lastname: Haymaker
authors.forename: Renu
authors.initials: R
authors.lastname: Jain
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Tartar
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hoeman
authors.forename: John C
authors.initials: JC
authors.lastname: Hardaway
authors.forename: Habib
authors.initials: H
authors.lastname: Zaghouani
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002678:Chimera / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000235:genetics; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D006023:Glycoproteins; D007136:Immunoglobulins; D015848:Interleukin-5; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010455:Peptides; C047516:Plp1 protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55); C435023:myelin proteolipid protein (139-151)