Pathogenic aquaporin-4 reactive T cells are sufficient to induce mouse model of neuromyelitis optica

Melina Jones, Hwa Huang, Peter Calabresi, Michael Levy

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: Neuromyelitis Optica (NMO) is an autoimmune disease primarily targeting the spinal cord and optic nerve leading to paralysis and blindness. The discovery of an antibody against the astrocytic water channel, aquaporin-4 (AQP4), in the majority of patients, has led to the presumption that the antibody was necessary for disease pathogenesis. The potential role of T cells in the central nervous system, however, has not been thoroughly examined.

RESULTS: We generated an anti-AQP4 antibody seronegative model of NMO using pathogenic AQP4-reactive T cells in mice by immunizing AQP4 null mice with peptides corresponding to the second extracellular loop of AQP4, loop C. When polarized to a Th17 phenotype and transferred to wild-type mice, these cells caused tail and limb weakness. Histology showed demyelination and T cell infiltration in the spinal cord, optic nerve and brain. Animals receiving cells re-stimulated in culture with non-specific proteins resulted in no behavioral disease, indicating that specific targeting of AQP4 is essential for this phenotype.

CONCLUSIONS: In summary, we show that AQP4-reactive T cells are sufficient to trigger an NMO-like disease in mice, independent of antibodies, indicating that pathogenic AQP4-reactive T cells may play a similar role in humans.

Original languageEnglish (US)
Pages (from-to)28
Number of pages1
JournalActa neuropathologica communications
Volume3
DOIs
StatePublished - May 21 2015

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Aquaporin 4
Neuromyelitis Optica
T-Lymphocytes
Antibodies
Optic Nerve
Spinal Cord
Phenotype
Spinal Nerves
Aquaporins
Demyelinating Diseases
Blindness
Paralysis
Autoimmune Diseases
Tail
Histology
Extremities
Central Nervous System
Peptides

ASJC Scopus subject areas

  • Medicine(all)

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Pathogenic aquaporin-4 reactive T cells are sufficient to induce mouse model of neuromyelitis optica. / Jones, Melina; Huang, Hwa; Calabresi, Peter; Levy, Michael.

In: Acta neuropathologica communications, Vol. 3, 21.05.2015, p. 28.

Research output: Contribution to journalArticle

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