Characterization of the T cell receptor repertoire in the Japanese neuromyelitis optica: T cell activity is up-regulated compared to multiple sclerosis

Warabi, Yoko; Yagi, Kohichi; Hayashi, Hideaki; Matsumoto, Yoh

doi:10.1016/j.jns.2006.06.011

Cited by 28 publications

(23 citation statements)

References 23 publications

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“…The presence of T cells within active NMO lesions [2], evidence for clonal T cell expansion in peripheral blood of NMO patients [31], and the observations that AQP4-specific antibodies from NMO patients were not pathogenic in rats in the absence of CNS inflammation provide indirect evidence suggesting that T cells may participate in the etiology of NMO. Knowing that AQP4-specific antibodies in NMO serum are T-cell dependent IgG (IgG1) points to antigen-specific CD4 + T cell-mediation of its humoral response.…”

Section: Resultsmentioning

confidence: 99%

Immunodominant T Cell Determinants of Aquaporin-4, the Autoantigen Associated with Neuromyelitis Optica

et al. 2010

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Autoantibodies that target the water channel aquaporin-4 (AQP4) in neuromyelitis optica (NMO) are IgG1, a T cell-dependent Ig subclass. However, a role for AQP4-specific T cells in this CNS inflammatory disease is not known. To evaluate their potential role in CNS autoimmunity, we have identified and characterized T cells that respond to AQP4 in C57BL/6 and SJL/J mice, two strains that are commonly studied in models of CNS inflammatory diseases. Mice were immunized with either overlapping peptides or intact hAQP4 protein encompassing the entire 323 amino acid sequence. T cell determinants identified from examination of the AQP4 peptide (p) library were located within AQP4 p21-40, p91-110, p101-120, p166-180, p231-250 and p261-280 in C57BL/6 mice, and within p11-30, p21-40, p101-120, p126-140 and p261-280 in SJL/J mice. AQP4-specific T cells were CD4+ and MHC II-restricted. In recall responses to immunization with intact AQP4, T cells responded primarily to p21-40, indicating this region contains the immunodominant T cell epitope(s) for both strains. AQP4 p21-40-primed T cells secreted both IFN-γ and IL-17. The core immunodominant AQP4 21-40 T cell determinant was mapped to residues 24-35 in C57BL/6 mice and 23-35 in SJL/J mice. Our identification of the AQP4 T cell determinants and characterization of its immunodominant determinant should permit investigators to evaluate the role of AQP4-specific T cells in vivo and to develop AQP4-targeted murine NMO models.

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Section: Resultsmentioning

confidence: 99%

Immunodominant T Cell Determinants of Aquaporin-4, the Autoantigen Associated with Neuromyelitis Optica

et al. 2010

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“…32,58 Alternatively, the strong IgG response against AQP-4 in NMO patients suggests that they may mount a potentially encephalitogenic T-cell response against this antigen itself. Whether this is the case is currently unresolved, but clonal expansion of T cells, previously described to occur in the peripheral blood of NMO patients, 59 indicates that T-cell responses may be involved in the pathogenesis of this disease.…”

Section: Fig 6 Aquaporin-4 (Aqp-4) Is Not Targeted By Human Anti-aqpmentioning

confidence: 99%

Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo

Bradl

Misu

Takahashi

et al. 2009

Annals of Neurology

516

500

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“…Further evidence for a critical role of T cells in NMO comes from observations in Japanese NMO patients, where T cell receptors using the Vβ1 or Vβ13 chain were clonally expanded [38]. T cell recognize “their” specific antigen in context with major histocompatibility complex (MHC) class I or II products, which show an association with NMO in some patient cohorts.…”

Section: Introductionmentioning

confidence: 99%

Pathogenic T cell responses against aquaporin 4

et al. 2011

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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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-011-0824-0) contains supplementary material, which is available to authorized users.

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Characterization of the T cell receptor repertoire in the Japanese neuromyelitis optica: T cell activity is up-regulated compared to multiple sclerosis

Cited by 28 publications

References 23 publications

Immunodominant T Cell Determinants of Aquaporin-4, the Autoantigen Associated with Neuromyelitis Optica

Immunodominant T Cell Determinants of Aquaporin-4, the Autoantigen Associated with Neuromyelitis Optica

Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo

Pathogenic T cell responses against aquaporin 4

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