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• W1997531461 abstract "Over the past decade, considerable attention has focused on the theory that MS is an autoimmune disease mediated by T cells specific for neural autoantigens. [1,2] Infectious agents may play a role in triggering an autoimmune process in a susceptible individual. [3,4] If so, this would reconcile the roles of environmental and genetic factors in the development of MS. The existence of structural similarities between viral antigens and autoantigens (viral mimicry) and the possibility that viral products (super antigens) can amplify T-cell populations have suggested mechanisms by which an infectious agent such as a virus can initiate an autoimmune process. [5,6] An essential element of both hypotheses (molecular mimicry and superantigens) is the expansion and targeting of autoreactive CD4+ T cells to the CNS. Hence, understanding T-cell receptor (TCR) gene usage of autoreactive T cells and their cytokine secretion profile has been a central focus of interest. We propose a model of CNS demyelination that is not predicated upon the continued presence of autoreactive T cells. Instead, we suggest that microglial activation is a central element in CNS demyelination and that the oligodendrocyte-myelin unit is the target. Understanding the nature of microglial activation is likely to offer therapeutic insights to the treatment of MS.In contrast to autoantibody-mediated autoimmune disease, evidence for the role of autoreactive T cells in autoimmune disease has been difficult to prove. This is in part because T-cell reactivity to autoantigens is present in the normal healthy population and there is no system to test the pathogenicity of autoreactive T cells. Nonetheless, rheumatoid arthritis, MS, inflammatory bowel disease, and insulin-dependent diabetes mellitus are thought to represent T-cell-mediated autoimmune disease. In this paradigm, the end-organ damage is not the result of antibodies to self-antigens but due in part to a delayed type hypersensitivity, cytokines, and cytotoxic T-cell …" @default.
• W1997531461 created "2016-06-24" @default.
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• W1997531461 date "1997-02-01" @default.
• W1997531461 modified "2023-10-08" @default.
• W1997531461 title "Indictment of the microglia as the villain in multiple sclerosis" @default.
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• W1997531461 doi "https://doi.org/10.1212/wnl.48.2.464" @default.
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