title: Resetting autoimmunity in the nervous system: The role of hematopoietic stem cell transplantation.
abstract: According to current concepts for multiple sclerosis (MS), a fundamental pathogenic role is played by T- and B-cells that inappropriately recognize self antigens and initiate a cell-mediated or humoral inflammatory reaction that injures myelin and axons, and results in neural dysfunction and loss. Transplantation of bone marrow-derived hematopoietic stem cells following high-dose immunosuppression is being evaluated as an experimental treatment for severe forms of immune-mediated disorders, including MS. The primary goal of this therapeutic approach is to induce medication-free remission from new disease activity by correcting the immune aberrations that promote the attack against self tissue; this approach is termed 'immune repair'. In this review, the clinical experience gained from the use of autologous hematopoietic stem cell transplantation in treating severe forms of MS are presented, and the current understanding of the mechanisms underlying the mode of action of this treatment, including depletion of disease-mediating immune cells, rejuvenation of the immune repertoire and improvement of regulatory cell function, is discussed.
authors.affiliation: Imperial College London, Centre for Neurosciences, Department of Medicine, Burlington Danes Building, Room E415, 160 Du Cane Road, London, W12 0NN, UK. p.muraro@imperial.ac.uk
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Muraro
authors.forename: Sofia V
authors.initials: SV
authors.lastname: Abrahamsson