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Journal of Neuroinflammation

, 10:887

First Online: 22 September 2013Received: 08 July 2013Accepted: 08 September 2013


BackgroundAutoimmunity to neuronal proteins occurs in several neurological syndromes, where cellular and humoral responses are directed to surface as well as intracellular antigens. Similar to myelin autoimmunity, pathogenic immune response to neuroaxonal components such as neurofilaments may contribute to neurodegeneration in multiple sclerosis.

MethodsWe studied the immune response to the axonal protein neurofilament light NF-L in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis. To examine the association between T cells and axonal damage, pathology studies were performed on NF-L immunized mice. The interaction of T cells and axons was analyzed by confocal microscopy of central nervous system tissues and T-cell and antibody responses to immunodominant epitopes identified in ABH H2-A and SJL-J H2-A mice. These epitopes, algorithm-predicted peptides and encephalitogenic motifs within NF-L were screened for encephalitogenicity.

ResultsConfocal microscopy revealed both CD4 and CD8 T cells alongside damaged axons in the lesions of NF-L immunized mice. CD4 T cells dominated the areas of axonal injury in the dorsal column of spastic mice in which the expression of granzyme B and perforin was detected. Identified NF-L epitopes induced mild neurological signs similar to the observed with the NF-L protein, yet distinct from those characteristic of neurological disease induced with myelin oligodendrocyte glycoprotein.

ConclusionsOur data suggest that CD4 T cells are associated with spasticity, axonal damage and neurodegeneration in NF-L immunized mice. In addition, defined T-cell epitopes in the NF-L protein might be involved in the pathogenesis of the disease.

KeywordsNeurofilament light Axonal damage Neurodegeneration Experimental autoimmune encephalomyelitis Multiple sclerosis AbbreviationsBSABovine serum albumin

CNSCentral nervous system

CFAComplete Freund’s adjuvant

EAEExperimental autoimmune encephalomyelitis

mAbMonoclonal antibody

MHCMajor histocompatibility complex

MOGMyelin oligodendrocyte glycoprotein

MSMultiple sclerosis

NF-LNeurofilament light

PBSPhosphate-buffered saline

PCRPolymerase chain reaction

RTReverse transcriptase

SCHSpinal cord homogenate

SIStimulation index.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-2094-10-118 contains supplementary material, which is available to authorized users.

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Autor: Fabiola Puentes - Baukje J van der Star - Marion Victor - Markus Kipp - Cordian Beyer - Regina Peferoen-Baert - Kimberley 


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