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Autoimmune disease, such as multiple sclerosis, results from the breakdown of immune tolerance to self. The goal of therapy is to restore this state of tolerance and understanding how this may occur physiologically is important for improving intervention strategies. Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis in which disease is induced by immunisation with antigenic components of myelin. In B6 mice, the disease course is monophasic and mice spontaneously enter remission, providing an ideal scenario to study the natural restoration of tolerance. IL-10-deficient mice fail to recover from EAE, and it is thought that production of IL-10 within the CNS is particularly important for recovery. Previous work from the Anderton lab had also shown B cell production of the immunoregulatory cytokine IL-10 to be vital for recovery. The aim of this PhD was to further investigate the role of IL-10 producing B cells and CD4+ T cells during remissions from EAE. It was found that while B cells clearly play an important role in recovery, and post-recovery B cells can transfer protection to naïve recipients, these B cells do not localise to the CNS. Instead, IL-10 producing CD4+ cells bearing phenotypic markers and functional characteristics of regulatory T cells were found to accumulate in the CNS during recovery. Depletion of CD25+ cells in vivo resulted in impaired recovery, and transfer of CD4+CD25+ cells from the CNS of mice with EAE protected recipients, further confirming a functional role for these cells. Thus, dual cellular regulation occurs during recovery from EAE, with B cells acting in secondary lymphoid sites and CD4+CD25+ cells acting at the effector site.