التفاصيل البيبلوغرافية
| العنوان: |
Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen. |
| المؤلفون: |
Kinzel, Silke, Lehmann-Horn, Klaus, Torke, Sebastian, Häusler, Darius, Winkler, Anne, Stadelmann, Christine, Payne, Natalie, Feldmann, Linda, Saiz, Albert, Reindl, Markus, Lalive, Patrice, Bernard, Claude, Brück, Wolfgang, Weber, Martin |
| 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] |
|
Copyright of Acta Neuropathologica is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
