التفاصيل البيبلوغرافية
| العنوان: |
Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen. |
| المؤلفون: |
Kinzel, Silke1, Lehmann-Horn, Klaus2, Torke, Sebastian1, Häusler, Darius1, Winkler, Anne1, Stadelmann, Christine1, Payne, Natalie3, Feldmann, Linda1, Saiz, Albert4, Reindl, Markus5, Lalive, Patrice, Bernard, Claude3, Brück, Wolfgang1, Weber, Martin martin.weber@med.uni-goettingen.de |
| المصدر: |
Acta Neuropathologica. Jul2016, Vol. 132 Issue 1, p43-58. 16p. |
| مصطلحات موضوعية: |
*CENTRAL nervous system, *T cells, *AUTOIMMUNE diseases, *NEURODEGENERATION, *MULTIPLE sclerosis |
| مستخلص: |
In the pathogenesis of central nervous system (CNS) demyelinating disorders, antigen-specific B cells are implicated to act as potent antigen-presenting cells (APC), eliciting waves of inflammatory CNS infiltration. Here, we provide the first evidence that CNS-reactive antibodies (Ab) are similarly capable of initiating an encephalitogenic immune response by targeting endogenous CNS antigen to otherwise inert myeloid APC. In a transgenic mouse model, constitutive production of Ab against myelin oligodendrocyte glycoprotein (MOG) was sufficient to promote spontaneous experimental autoimmune encephalomyelitis (EAE) in the absence of B cells, when mice endogenously contained MOG-recognizing T cells. Adoptive transfer studies corroborated that anti-MOG Ab triggered activation and expansion of peripheral MOG-specific T cells in an Fc-dependent manner, subsequently causing EAE. To evaluate the underlying mechanism, anti-MOG Ab were added to a co-culture of myeloid APC and MOG-specific T cells. At otherwise undetected concentrations, anti-MOG Ab enabled Fc-mediated APC recognition of intact MOG; internalized, processed and presented MOG activated naïve T cells to differentiate in an encephalitogenic manner. In a series of translational experiments, anti-MOG Ab from two patients with an acute flare of CNS inflammation likewise facilitated detection of human MOG. Jointly, these observations highlight Ab-mediated opsonization of endogenous CNS auto-antigen as a novel disease- and/or relapse-triggering mechanism in CNS demyelinating disorders. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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