ABSTRACT
Acute, high-dose immunosuppression, followed by a haematopoietic stem cell rescue (autologous bone marrow transplantation) has proved effective in various experimental models of autoimmunity. The rationale for such an approach in autoimmune diseases is based on the concept of de novo immune system reconstitution, which (in the presence of the auto-antigens in the thymus) may re-induce the defective self-tolerance. Our previous work has shown that in experimental autoimmune encephalomyelitis (EAE), autologous or syngeneic bone marrow transplantation not only prevents the appearance of paralytic signs, but can also partially reverse chronic disease and induce long-term, antigenspecific tolerance. However, there are serious reservations to be considered when interpreting these data and before applying similar protocols in patients with multiple sclerosis. First, the model of EAE is not a completely reliable model of multiple sclerosis (MS). Second, in animals with chronic EAE, although further relapses were prevented, the established paralysis was usually not reversible. According to recent data, in chronic MS lesions the damage caused by axonal loss/transection and cortical/spinal cord atrophy is irreversible and, probably, not amenable to immunotherapy. Third, long-term, antigenspecific tolerance may be induced by bone marrow transplantation, but not in all cases; in passively induced chronic relapsing EAE (CR-EAE) many of the mice relapsed upon challenge with myelin antigens, which may indicate that the presence of the immunizing, myelin antigens (on the site of immunization) during the process of immune reconstitution is critical for induction of tolerance. Finally, one should weigh the procedure-related risks (including mortality of up to 5%) of bone marrow or peripheral stem cell transplantation.
