Protective autoimmunity and neuroprotection in inflammatory and noninflammatory neurodegenerative diseases
Section snippets
Multiple sclerosis: a failure of protective autoimmunity?
Multiple sclerosis (MS) is a relatively common autoimmune-related neurological disorder in young adults (for review see [1]). MS has long been viewed as a chronic inflammatory disease in which the patient's own immune cells mediate damage to myelin, and the resulting demyelination causes neuronal dysfunction, leading to neuronal loss [2], [3].
The etiology of MS is unclear [4], [5]. In patients with MS, sites of central nervous system (CNS) lesions, or plaques, contain T cells of different
Is the regulation that is needed for avoidance of autoimmune disease related to the regulation needed for protective autoimmunity?
Today we know that T cells circulate in the bloodstream both of individuals that are susceptible and of individuals that are resistant to autoimmune diseases, and that their presence in the circulation probably reflects not an escape from selection, but rather a positive selection of such clones in the thymus [41]. Autoreactive T cells are primed in the thymus and then released to the periphery. Myelin-specific proteins are now known to be expressed in the thymus [42], [43], [44].
Knowing that
Therapeutic implications: a paradigm shift
The perception of autoimmunity as the body's protective mechanism, at least in the CNS, and of autoimmune disease as a failure of protective autoimmunity, calls for therapeutic protocols to be revisited. For treatment of autoimmune diseases, our findings argue in favor of therapies based on immunomodulation rather than immunosuppression, with the object of maximizing the beneficial component rather than eliminating the immune effect altogether [38]. For treatment of CNS damage not caused by
Acknowledgments
We thank S.R. Smith for editing the manuscript. M.S. holds the Maurice and Ilse Katz Professorial Chair in Neuroimmunology. The work was supported by Proneuron Ltd., Industrial Park, Ness-Ziona, Israel and in part by grants from The Glaucoma Research Foundation and The Alan Brown Foundation for Spinal Cord Injury awarded to M.S.
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