Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen
2016 | journal article. A publication with affiliation to the University of Göttingen.
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Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen
Kinzel, S.; Lehmann-Horn, K.; Torke, S.; Haeusler, D.; Winkler, A.; Stadelmann, C. & Payne, N. L. et al. (2016)
Acta Neuropathologica, 132(1) pp. 43-58. DOI: https://doi.org/10.1007/s00401-016-1559-8
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Details
- Authors
- Kinzel, Silke; Lehmann-Horn, Klaus; Torke, Sebastian; Haeusler, Darius; Winkler, Anne; Stadelmann, Christine ; Payne, Natalie L.; Feldmann, Linda; Saiz, Albert; Reindl, Markus; Lalive, Patrice H.; Bernard, Claude C.; Brueck, Wolfgang; Weber, Martin S.
- Abstract
- 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 na < ve 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.
- Issue Date
- 2016
- Status
- published
- Publisher
- Springer
- Journal
- Acta Neuropathologica
- ISSN
- 1432-0533; 0001-6322