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Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy

Abstract

Autoimmunity to antigens of the central nervous system is usually considered detrimental. T cells specific to a central nervous system self antigen, such as myelin basic protein, can indeed induce experimental autoimmune encephalomyelitis, but such T cells may nevertheless appear in the blood of healthy individuals. We show here that autoimmune T cells specific to myelin basic protein can protect injured central nervous system neurons from secondary degeneration. After a partial crush injury of the optic nerve, rats injected with activated anti–myelin basic protein T cells retained approximately 300% more retinal ganglion cells with functionally intact axons than did rats injected with activated T cells specific for other antigens. Electrophysiological analysis confirmed this finding and suggested that the neuroprotection could result from a transient reduction in energy requirements owing to a transient reduction in nerve activity. These findings indicate that T–cell autoimmunity in the central nervous system, under certain circumstances, can exert a beneficial effect by protecting injured neurons from the spread of damage.

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Figure 1: T–cell presence in injured optic nerve 1 week after injury.
Figure 2: T cells specific to MBP, but not to OVA or p277 of hsp60, protect neurons from secondary degeneration.
Figure 3: Photomicrographs of retrogradely labeled retinas of injured optic nerves of rats.
Figure 4: a, Clinical severity of EAE is not influenced by an optic nerve crush injury.
Figure 5: T cells specific to p51–70 of MBP protect neurons from secondary degeneration.
Figure 6: Anti–MBP T cells increase the CAP amplitude of injured optic nerves.

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Acknowledgements

We thank S. Smith and P. Taylor for editorial assistance, and I. Friedmann for help with graphics. I.R. Cohen is the incumbent of the Mauerberger Chair in Immunology, the director of the Robert Koch–Minerva Center for Research in Autoimmune Disease and the director of the Center for the Study of Emerging Diseases. M.S. holds the Maurice and Ilse Katz Professorial Chair in Neuroimmunology.

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Correspondence to Michal Schwartz.

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Moalem, G., Leibowitz–Amit, R., Yoles, E. et al. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5, 49–55 (1999). https://doi.org/10.1038/4734

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