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Summary
Current concepts attribute an early and central role for auto-aggressive, myelin-specific
T-lymphocytes in the pathogenesis of multiple sclerosis. This view emerged from immunological
and pathological findings in experimental autoimmune encephalitis, an animal model
characterised by pathological lesions closely resembling the ones found in multiple
sclerosis. Furthermore, therapeutic strategies targeting the functions of these encephalitogenic
T cells which attenuate their pathogenicity such as glatiramer acetate or anti-VLA4
antibody treatments represent proven approaches in multiple sclerosis. Nonetheless,
all therapies evaluated to date either insufficiently dampen down inflammation or
completely block immune processes. For this reason, there is a need to identify new
therapeutic targets. We have employed live intravital two-photon microscopy to learn
more about the behaviour of T cells during the preclinical phase of EAE, when T cells
acquire the properties required to invade their target organ. Furthermore, we were
able to identify an unexpected locomotive behaviour of T cells at the blood–brain
barrier, which occurs immediately before diapedesis and the induction of paralytic
disease. Such studies might open new avenues for the treatment of CNS autoimmune diseases.
Multiple sclerosis is considered to be an autoimmune disease in which self-reactive
T cells enter the central nervous system (CNS) and create an inflammatory milieu that
destroys myelin and neurons. Immunomodulatory strategies for the treatment of multiple
sclerosis target this process by attempting to inactivate these auto-aggressive T
cells. However, so far, these strategies have failed to extinguish disease activity
completely. For this reason, there is a need to understand in more detail the mechanisms
by which T cells become encephalitogenic, how they enter the nervous system, and what
the signals are that guide them along this path. If these processes could be better
understood, it may be possible to design more effective and specific therapies for
multiple sclerosis. This article will give a brief overview about our recent findings
obtained using intravital imaging of autoaggressive effector T cells in an experimental
model of multiple sclerosis. This new technological approach might help to fill some
gaps in the understanding of autoimmune pathogenesis of multiple sclerosis.
Keywords
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