Pathogenic T cell responses against aquaporin 4
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Maria Pohl Marie-Therese Fischer Simone Mader Kathrin Schanda Maja Kitic Rakhi Sharma Isabella Wimmer Tatsuro Misu Kazuo Fujihara Mark
- چاپ و سال / کشور: 2011
Description
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 patientderived aquaporin-4-specific antibodies is induced in kidney cells by the pro-inflammatory cytokine gammainterferon. 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.
Acta Neuropathol (2011) 122:21–34 DOI 10.1007/s00401-011-0824-
