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Autoimmunity

A new target in multiple sclerosis?

Nature Reviews Immunology volume 9, pages 390–391 (2009)Cite this article

To investigate the possibility that contactin 2 acts as an autoantigen in patients with multiple sclerosis, the authors examined the proliferative responses of peripheral blood mononuclear cells incubated with contactin 2. Cells from patients with multiple sclerosis showed higher levels of proliferation in response to contactin 2 compared with healthy controls ex vivo. Furthermore, a high percentage of cells from patients with multiple sclerosis secreted interferon-γ ex vivo in response to contactin 2, and some cells secreted interleukin-17; both cytokine responses were markedly increased following in vitro restimulation with the autoantigen. Based on these observations, the authors concluded that patients with multiple sclerosis develop T cell responses to contactin 2.

The secretion of cytokines by T cells following incubation with contactin 2 suggested that this response could contribute to disease pathogenesis. Indeed, adoptive transfer of T cells specific for the rat contactin 2 orthologue TAG1 (transient axonal glycoprotein 1) induced experimental autoimmune encephalomyelitis (EAE) in rats. Histological analysis revealed that inflammatory cell infiltrates were prominent in the cortex and grey matter of the spinal cord. Interestingly, this is in contrast to models of EAE caused by myelin oligodendrocyte glycoprotein (MOG)-specific T cells, in which inflammation is primarily localized in the white matter of the spinal cord. This indicates that T cell responses in patients with multiple sclerosis might be heterogeneous. Despite causing inflammation, the transfer of TAG1-specific T cells did not result in demyelination. However, administration of MOG-specific antibodies 6 days after T cell transfer increased disease severity, which was associated with marked demyelination; this could be indicative of the ability of TAG1-specific T cells to compromise the blood–brain barrier.

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ORIGINAL RESEARCH PAPER

  1. Derfuss, T. et al. Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc. Natl Acad. Sci. USA 28 Apr 2009 (doi:10.1073/pnas.0901496106)

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  1. Rachel David
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David, R. A new target in multiple sclerosis?. Nat Rev Immunol 9, 390–391 (2009). https://doi.org/10.1038/nri2574

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  • DOI: https://doi.org/10.1038/nri2574

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