Regulatory lymphocytes are key factors in mhc-independent resistance to EAE

[Background and Objectives] 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. © 2014 Nieves Marín et al.This study was supported by PS09/01652 and PS09/01338 Grants from Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness, Spain, SAF2010/17501 from the Ministry of Science and Innovation, Spain, and “Ajuts per donar Suport als Grups de Recerca de Catalunya (2009 SGR 0793),” sponsored by the “Agència de Gestió d’Ajuts Universitaris i de Recerca” (AGAUR), Generalitat de Catalunya, Spain. Herena Eixarch is supported by the “Sara Borrell” program (CD09/00363), Nieves Marín and Miriam Mecha are supported by Red Española de Esclerosis Múltiple (REEM, RD 07/0060 and RD12/0032), and Carmen Espejo was partially supported by the “Miguel Servet” program (CP07/00146, CPII13/00028), all of them of the FIS, Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain.Peer Reviewe