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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-31855

Sobottka, B; Harrer, M D; Ziegler, U; Fischer, K; Wiendl, H; Hünig, T; Becher, B; Goebels, N (2009). Collateral bystander damage by myelin-directed CD8+ T cells causes axonal loss. American Journal of Pathology, 175(3):1160-1166.

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Permanent disability of patients suffering from central nervous system (CNS) inflammation such as multiple sclerosis, the most common chronic inflammatory disorder of the CNS, originates mainly from demyelination and axonal damage. Although many studies in the past focused on the role of CD4(+) T cells, several recent findings postulate the relevance of autoaggressive, cytotoxic CD8(+) T cells in the effector phase of multiple sclerosis. Yet, it remains unresolved whether axonal injury is the result of a CD8(+) T cell-targeted hit against the axon itself or the consequence of an attack against the myelin structure. To address this issue of CD8-mediated tissue damage in CNS inflammation, we performed continuous confocal imaging of autoaggressive, cytotoxic CD8(+) T cells in living organotypic cerebellar brain slices. We observed that loading brain slices with the cognate peptide antigen caused CD8-mediated damage of myelinated axons. To exclude the possibility that the cognate peptide loaded onto the brain slices was presented by axons directly, we restricted the cognate antigen expression exclusively to the cytosol of oligodendrocytes. Aside from vast myelin damage, extensive axonal bystander injury occurred. Using this model system of inflammatory CNS injury, we visualize that axonal loss can be the consequence from "collateral bystander damage" by autoaggressive, cytotoxic CD8(+) T cells, targeting their cognate antigen processed and presented by oligodendrocytes.


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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Microscopy and Image Analysis
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:20 Feb 2010 18:45
Last Modified:05 Apr 2016 13:59
Publisher DOI:10.2353/ajpath.2009.090340
PubMed ID:19700745

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