International Immunology Advance Access originally published online on February 24, 2009
International Immunology 2009 21(4):433-441; doi:10.1093/intimm/dxp011
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T-cell responses to neurofilament light protein are part of the normal immune repertoire
1 Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands
2 Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
3 Department of Neurology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
4 Department of Pathology, MS Centre, VU University Medical Centre, Amsterdam, The Netherlands
5 Neuroimmunology Unit, Neuroscience Centre, Institute of Cell and Molecular Science, Queen Mary University of London, London, UK
Correspondence to: S. Amor; E-mail: s.amor{at}vumc.nl
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system in which axonal damage and degeneration contribute significantly to the progressive irreversible neurological disability. Similar to pathogenic myelin autoimmunity, autoimmune responses to neuronal antigens may contribute to axonal damage and irreversible disability in MS. Auto-antibodies to the axonal cytoskeletal protein neurofilament light (NF-L) are associated with cerebral atrophy in MS and we have recently reported that NF-L autoimmunity is pathogenic in mice. However, the T-cell response to NF-L in MS patients has not been examined. Here, we identify and characterize T-cell proliferative responses to NF-L as compared with myelin oligodendrocyte glycoprotein (MOG) in MS patients and healthy controls. Using a carboxyfluorescein succinimidyl ester dilution assay, we show that while responses to MOG are dominated by CD3+CD4+ T cells, responses to NF-L were observed in both CD3+CD4+ and CD3+CD8+ T-cell populations. Both MOG- and NF-L-reactive cells expressed CD45RO+, indicative of a memory phenotype. Moreover, in contrast to MOG stimulation which predominantly induced IFN-
, both Th1- and Th2-type T-cell responses to NF-L were observed as indicated by the induction of IFN-, tumor necrosis factor-
as well as IL-4. The finding of T-cell responses to NF-L in MS patients may reflect transient activation of pathogenic potential but their presence also in healthy controls indicates that these cells are part of the normal immune repertoire.
Keywords: autoimmunity, axonal damage, multiple sclerosis, neurodegeneration, neuronal antigens
*Affiliations 1, 2 and 3 are all part of the MS Centre ErasMS
Received 5 April 2008, accepted 27 January 2009.