title: Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is an autoimmune disorder in which activated T cells cross the blood-brain barrier (BBB) to initiate an inflammatory response that leads to demyelination and axonal damage. The key mechanisms responsible for disease initiation are still unknown. We addressed this issue in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is widely known that EAE manifests only in certain strains when immunized with myelin proteins or peptides. We studied the differential immune responses induced in two mouse strains that are susceptible or resistant to EAE induction when they are immunized with the 139-151 peptide of proteolipid protein, an encephalitogenic peptide capable of inducing EAE in the susceptible strain. The adequate combination of major histocompatibility complex alleles and myelin peptides triggered in susceptible mice a T helper type 17 (Th17) response capable of inducing the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies. These were not detected in resistant mice, despite immunization with the encephalitogenic peptide in junction with complete Freund's adjuvant and pertussis toxin, which mediate BBB disruption. These data show the pivotal role of Th17 responses and of high-affinity anti-myelin antibodies in EAE induction and that mechanisms that prevent their appearance can contribute to resistance to EAE.
authors.affiliation: Multiple Sclerosis Unit, Immunology and Neurology Departments, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain; Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Marín
authors.forename: H
authors.initials: H
authors.lastname: Eixarch
authors.forename: M J
authors.initials: MJ
authors.lastname: Mansilla
authors.forename: E
authors.initials: E
authors.lastname: Rodríguez-Martín
authors.forename: M
authors.initials: M
authors.lastname: Mecha
authors.forename: C
authors.initials: C
authors.lastname: Guaza
authors.forename: J C
authors.initials: JC
authors.lastname: Álvarez-Cermeño
authors.forename: X
authors.initials: X
authors.lastname: Montalban
authors.forename: L M
authors.initials: LM
authors.lastname: Villar
authors.forename: C
authors.initials: C
authors.lastname: Espejo
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009103:Multiple Sclerosis / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D007074:Immunoglobulin G; D020381:Interleukin-17; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C047516:Plp1 protein, mouse; C435023:myelin proteolipid protein (139-151)
keywords: anti-myelin antibodies; experimental autoimmune encephalomyelitis; immune response; multiple sclerosis