Open Access Research

Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis

Fabiola Puentes1*, Baukje J van der Star2, Marion Victor3, Markus Kipp3, Cordian Beyer3, Regina Peferoen-Baert2, Kimberley Ummenthum2, Gareth Pryce1, Wouter Gerritsen2, Ruth Huizinga4, Arie Reijerkerk5, Paul van der Valk2, David Baker1 and Sandra Amor12

Author Affiliations

1 Neuroimmunology Unit, Blizard Institute, Bart’s and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK

2 Pathology Department, VU University Medical Center, Amsterdam, The Netherlands, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

3 Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Aachen 52062, Germany

4 Department of Immunology, Erasmus MC, University Medical Center, Rotterdam 3062 PA, The Netherlands

5 Molecular Cell Biology and Immunology Department, VU Medical Center, Amsterdam, The Netherlands, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

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Journal of Neuroinflammation 2013, 10:118  doi:10.1186/1742-2094-10-118

Published: 22 September 2013

Abstract

Background

Autoimmunity 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.

Methods

We 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-Ag7) and SJL/J (H2-As) mice. These epitopes, algorithm-predicted peptides and encephalitogenic motifs within NF-L were screened for encephalitogenicity.

Results

Confocal 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.

Conclusions

Our 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.

Keywords:
Neurofilament light; Axonal damage; Neurodegeneration; Experimental autoimmune encephalomyelitis; Multiple sclerosis