engleski

Prevention of experimental autoimmune encephalomyelitis by administration of myelin basic protein in rats

Background and Purpose: Experimental autoimmune encephalomyelitis (EAE) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS). It is also the most used animal model for human disease of multiple sclerosis (MS). One of therapeutic approaches to MS is administration of myelin basic protein (MBP). The purpose of this investigation was to determine the occurrence and mechanisms of unresponsiveness to EAE induction in rats by MBP administration. The cellular mechanism of tolerance was investigated by adoptive transfer of lymph node and bone marrow cells in thymectomized, irradiated rats, reconstituted with bone marrow cells (TIR). Material and Methods: EAE was induced by injecting the encephalogenic vaccine (EV) into Lewis and Wistar rats. They were examined daily and incidence, mortality and clinical severity of disease were determined. To determine the optimal time for tolerance induction MBP was injected on the 8th and 3rd day before, or on the 6th day after induction of EAE. After adoptive transfer into TIR rats of MBP treated or untreated donors' lymph node or bone marrow cells, EAE was induced. Significance of results was tested with   analysis, Fischer's exact test and Student' s t test. Results: In both rat strains which received MBP on the 8th and 3rd day prior to EAE induction, the incidence and severity of EAE was significantly lower in comparison with controls. However, in those which received MBP on the 6th day after EAE induction there was no significant difference. In TIR rats EAE can not be induced. However, adaptive transfer of lymph node cells from untreated donors makes the host susceptible for EAE induction. In contrast, adoptive transfer of lymph node cells from MBP-pretreated donors to TIR rats couldn't transfer susceptibility to EAE induction. The transfer of bone marrow cells into TIR recipients doesn' t transfer susceptibility to EAE induction. Conclusion: Specific immunological tolerance and prevention of EAE can be induced by administration of MBP before EAE induction. Unresponsiveness is mediated by several distinct, yet interacting mechanisms including the generation of suppressive T cells producing cytokines and the induction of clonal anergy and/or deletion.

experimental autoimune encephalpmyelitis; EAE; multiple sclerosis; myeline basic proteine; immune tolerance

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