Journal
ACTA NEUROPATHOLOGICA
Volume 122, Issue 1, Pages 21-34Publisher
SPRINGER
DOI: 10.1007/s00401-011-0824-0
Keywords
EAE; Aquaporin-4; NMO; T cells
Categories
Funding
- European Union [LSHM-CT-2005-018637]
- Austrian Science Fund [P21581-B09]
- Austrian Science Fund
- Medical University Vienna
- interdisciplinary center for research and treatment (IFTZ) of Innsbruck Medical University [2007104]
- Ministry of Education, Culture, Sports, Science and Technology [19209032, 20390241, 22229008]
- Ministry of Health, Labor and Welfare of Japan
- Grants-in-Aid for Scientific Research [20390241, 19209032] Funding Source: KAKEN
- Austrian Science Fund (FWF) [P 21581] Funding Source: researchfish
- Austrian Science Fund (FWF) [P21581] Funding Source: Austrian Science Fund (FWF)
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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.
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