Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis.

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.

• Authors: Fabiola Puentes, Baukje J van der Star, Marion Victor, Markus Kipp, Cordian Beyer, Regina Peferoen-Baert, Kimberley Ummenthum, Gareth Pryce, Wouter Gerritsen, Ruth Huizinga, Arie Reijerkerk, Paul van der Valk, David Baker, Sandra Amor
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 10 Pg. 118 (Sep 22 2013) ISSN: 1742-2094 [Electronic] England
• PMID: 24053384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Epitopes, T-Lymphocyte
• Neurofilament Proteins
• neurofilament protein L

Topics

• Animals
• Autoantigens (immunology)
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology)
• Enzyme-Linked Immunosorbent Assay
• Epitopes, T-Lymphocyte (immunology)
• Female
• Immunohistochemistry
• Male
• Mice
• Microscopy, Confocal
• Neurofilament Proteins (immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Spinal Cord (immunology, pathology)
• T-Lymphocytes