title: Tolerance induction in experimental autoimmune encephalomyelitis using non-myeloablative hematopoietic gene therapy with autoantigen.
abstract: Experimental autoimmune encephalomyelitis (EAE) constitutes a paradigm of antigen (Ag)-specific T cell driven autoimmune diseases. In this study, we transferred bone marrow cells (BMCs) expressing an autoantigen (autoAg), the peptide 40-55 of the myelin oligodendrocytic glycoprotein (MOG(40-55)), to induce preventive and therapeutic immune tolerance in a murine EAE model. Transfer of BMC expressing MOG(40-55) (IiMOG-BMC) into partially myeloablated mice resulted in molecular chimerism and in robust protection from the experimental disease. In addition, in mice with established EAE, transfer of transduced BMC with or without partial myeloablation reduced the clinical and histopathological severity of the disease. In these experiments, improvement was observed even in the absence of engraftment of the transduced hematopoietic cells, probably rejected due to the previous immunization with the autoAg. Splenocytes from mice transplanted with IiMOG-BMC produced significantly higher amounts of interleukin (IL)-5 and IL-10 upon autoAg challenge than those of control animals, suggesting the participation of regulatory cells. Altogether, these results suggest that different tolerogenic mechanisms may be mediating the preventive and the therapeutic effects. In conclusion, this study demonstrates that a cell therapy using BMC expressing an autoAg can induce Ag-specific tolerance and ameliorate established EAE even in a nonmyeloablative setting.
authors.affiliation: Centre de Teixits i Teràpia Cel.lular, Banc de Sang i Teixits, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Herena
authors.initials: H
authors.lastname: Eixarch
authors.forename: Carmen
authors.initials: C
authors.lastname: Espejo
authors.forename: Alba
authors.initials: A
authors.lastname: Gómez
authors.forename: María José
authors.initials: MJ
authors.lastname: Mansilla
authors.forename: Mireia
authors.initials: M
authors.lastname: Castillo
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.forename: Francisco
authors.initials: F
authors.lastname: Vidal
authors.forename: Ramón
authors.initials: R
authors.lastname: Gimeno
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Jordi
authors.initials: J
authors.lastname: Barquinero
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D012190:Retroviridae
chemical_list: D001324:Autoantigens; D015848:Interleukin-5; D018992:Myelin-Associated Glycoprotein; D016753:Interleukin-10