Pathogenic T cell responses against aquaporin 4

Maria Pohl, Marie Therese Fischer, Simone Mader, Kathrin Schanda, Maja Kitic, Rakhi Sharma, Isabella Wimmer, Tatsuro Misu, Kazuo Fujihara, Markus Reindl, Hans Lassmann, Monika Bradl

Research output: Contribution to journalReview articlepeer-review

61 Citations (Scopus)

Abstract

Inflammatory lesions in the central nervous system of patients with neuromyelitis optica are characterized by infiltration of T cells and deposition of aquaporin-4-specific antibodies and complement on astrocytes at the glia limitans. Although the contribution of aquaporin-4-specific autoantibodies to the disease process has been recently elucidated, a potential role of aquaporin-4-specific T cells in lesion formation is unresolved. To address this issue, we raised aquaporin-4-specific T cell lines in Lewis rats and characterized their pathogenic potential in the presence and absence of aquaporin-4-specific autoantibodies of neuromyelitis optica patients. We show that aquaporin-4-specific T cells induce brain inflammation with particular targeting of the astrocytic glia limitans and permit the entry of pathogenic anti-aquaporin-4-specific antibodies to induce NMO-like lesions in spinal cord and brain. In addition, transfer of aquaporin-4-specific T cells provoked mild (subclinical) myositis and interstitial nephritis. We further show that the expression of the conformational epitope, recognized by NMO patient-derived aquaporin-4-specific antibodies is induced in kidney cells by the pro-inflammatory cytokine gamma-interferon. Our data provide further support for the view that NMO lesions may be induced by a complex interplay of T cell mediated and humoral immune responses against aquaporin-4.

Original languageEnglish
Pages (from-to)21-34
Number of pages14
JournalActa neuropathologica
Volume122
Issue number1
DOIs
Publication statusPublished - 2011 Jul

Keywords

  • Aquaporin-4
  • EAE
  • NMO
  • T cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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