Pathogenic T cell responses against aquaporin 4

Springer Science and Business Media LLC - Tập 122 - Trang 21-34 - 2011
Maria Pohl1, Marie-Therese Fischer1, Simone Mader2, Kathrin Schanda2, Maja Kitic1, Rakhi Sharma1, Isabella Wimmer1, Tatsuro Misu1, Kazuo Fujihara3, Markus Reindl2, Hans Lassmann1, Monika Bradl1
1Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria
2Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
3Department of Multiple Sclerosis Therapeutics and Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan

Tóm tắt

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.

Tài liệu tham khảo

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