Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis.
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.
Neuroimmunology Unit, Blizard Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. f.puentes@qmul.ac.uk.
Fabiola
F
Puentes
Baukje J
BJ
van der Star
Marion
M
Victor
Markus
M
Kipp
Cordian
C
Beyer
Regina
R
Peferoen-Baert
Kimberley
K
Ummenthum
Gareth
G
Pryce
Wouter
W
Gerritsen
Ruth
R
Huizinga
Arie
A
Reijerkerk
Paul
P
van der Valk
David
D
Baker
Sandra
S
Amor
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D016900:Neurofilament Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D016900:Neurofilament Proteins; C044882:neurofilament protein L