title: Regulatory lymphocytes are key factors in MHC-independent resistance to EAE.
abstract: OBJECTIVE
  Resistant and susceptible mouse strains to experimental autoimmune encephalomyelitis (EAE), an inducible demyelinating experimental disease serving as animal model for multiple sclerosis, have been described. We aimed to explore MHC-independent mechanisms inducing resistance to EAE.
  
  
  METHODS
  For EAE induction, female C57BL/6 (susceptible strain) and CD1 (resistant outbred strain showing heterogeneous MHC antigens) mice were immunized with the 35-55 peptide of myelin oligodendrocyte glycoprotein (MOG35-55). We studied T cell proliferation, regulatory and effector cell subpopulations, intracellular and serum cytokine patterns, and titers of anti-MOG serum antibodies.
  
  
  RESULTS
  Upon immunization with MOG35-55, T lymphocytes from susceptible mice but not that of resistant strain were capable of proliferating when stimulated with MOG35-55. Accordingly, resistant mice experienced a rise in regulatory B cells (P=0.001) and, to a lower extent, in regulatory T cells (P=0.02) compared with C57BL/6 susceptible mice. As a consequence, MOG35-55-immunized C57BL/6 mice showed higher percentages of CD4+ T cells producing both IFN-gamma (P=0.02) and IL-17 (P=0.009) and higher serum levels of IL-17 (P=0.04) than resistant mice.
  
  
  CONCLUSIONS
  Expansion of regulatory B and T cells contributes to the induction of resistance to EAE by an MHC-independent mechanism.
authors.affiliation: Multiple Sclerosis Unit, Immunology and Neurology Departments, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar Km 9.100, 28034 Madrid, Spain ; Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Marín
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain ; Neuroimmunology Group, Department of Functional and System Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Mecha
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain ; Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Passeig de la Vall d'Hebron 119-129, 08035 Barcelona, Spain ; Universitat Autònoma de Barcelona, Bellaterra, 08193 Cerdanyola del Vallès, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Espejo
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain ; Neuroimmunology Group, Department of Functional and System Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Leyre
authors.initials: L
authors.lastname: Mestre
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain ; Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Passeig de la Vall d'Hebron 119-129, 08035 Barcelona, Spain ; Universitat Autònoma de Barcelona, Bellaterra, 08193 Cerdanyola del Vallès, Spain.
authors.forename: Herena
authors.initials: H
authors.lastname: Eixarch
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain ; Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Passeig de la Vall d'Hebron 119-129, 08035 Barcelona, Spain ; Universitat Autònoma de Barcelona, Bellaterra, 08193 Cerdanyola del Vallès, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: Multiple Sclerosis Unit, Immunology and Neurology Departments, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar Km 9.100, 28034 Madrid, Spain ; Universitat Autònoma de Barcelona, Bellaterra, 08193 Cerdanyola del Vallès, Spain ; Department of Medicine, Universidad de Alcalá, Plaza de San Diego s/n, Alcalá de Henares, 28801 Madrid, Spain.
authors.forename: José C
authors.initials: JC
authors.lastname: Álvarez-Cermeño
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain ; Neuroimmunology Group, Department of Functional and System Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Guaza
authors.affiliation: Multiple Sclerosis Unit, Immunology and Neurology Departments, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar Km 9.100, 28034 Madrid, Spain ; Red Española de Esclerosis Múltiple (REEM), RETICS, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Villar
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology*
chemical_list: D057134:Antibodies, Neutralizing; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma