Open Access

Multiple sclerosis (MS) and stroke share a number of mechanisms of neuronal damage. In both cases the balance between neurodestruction and neuroprotection appears modulated by the function of the adaptive immune system. MS is a chronic inflammatory disease of the central nervous system (CNS), leading to permanent disability. It seems certain that an autoimmune response directed against the CNS is central to the pathogenesis of the disease. While these CNS-specific T cells are activated in MS patients, they are inactive and naive in healthy. Therefore it is believed that an activation of autoreactive T cells by cross-reactivity with pathogens occurs outside of the CNS. In consequence T cells express adhesion molecules and proteinases which enable them to cross the blood-brain barrier. In stroke, however, the blood-brain barrier is disturbed in its integrity caused by the decreased blood flow. Cells can freely migrate from the periphery into the brain. CNS autoreactive cells from the periphery can be activated within the CNS and thus contribute to further tissue damage. While the local autoimmune response remains temporary in stroked brains, it is chronically destroyed in MS. The differences between the underlying mechanisms are not understood. This thesis investigated T cell responses in Multiple Sclerosis in response to the therapeutics Mitoxantrone and IFN-b. The induction of a TH1 to TH2 cytokine response appears to be a shared mechanism of action between both therapeutic agents. Primarily the post stroke immune response was investigated. Patients developed a stroke induced immune suppression characterized by monocytic dysfunction and lymphocytopenia explaining the high frequency of post stroke infections. Moreover early post stroke predictors of subsequent infections, like the CD4+ T cell count, were identified. The T cell response of stroke patients appeared primed to proinflammation and unsuppressed after mitogen stimulation. A detailed understanding of post stroke immune alterations may offer new avenues of intervention to improve the clinical fate of stroke victims. In addition, such knowledge could also further our understanding of Multiple Sclerosis, because, while increasing the infection risk, the dampening of the immune system could have an important protective function, if it limits autoimmune brain damage triggered by the massive release of brain antigens during stroke. If these two pathways could be modulated separately it would create the opportunity to develop distinct therapeutic approaches that inhibit autoimmunity and strengthen antibacterial defenses. To further delineate these mechanisms it is crucial to investigate the role of the innate immune system as compared to the adaptive immune system in stroke induced immune suppression.