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Journal Article

T cell-activation in neuromyelitis optica lesions plays a role in their formation

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Kawakami,  Naoto
Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

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Wekerle,  Hartmut
Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

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Citation

Pohl, M., Kawakami, N., Kitic, M., Bauer, J., Martins, R., Fischer, M.-T., et al. (2013). T cell-activation in neuromyelitis optica lesions plays a role in their formation. Acta Neuropathologica Communications, 1: 85. doi:10.1186/2051-5960-1-85.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0015-840E-B
Abstract
Background: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS), which is characterized by the presence of pathogenic serum autoantibodies against aquaporin 4 (AQP4) in the vast majority of patients. The contribution of T cells to the formation of astrocyte destructive lesions is currently unclear. However, active human NMO lesions contain CD4+ T-lymphocytes expressing the activation marker Ox40, and the expression is more profound compared to that seen in MS lesions of comparable activity. Therefore, we analyzed the role of T-cell activation within the CNS in the initiation of NMO lesions in an experimental model of co-transfer of different encephalitogenic T-cells and human AQP4 antibody containing NMO immunoglobulin (NMO IgG). We further studied the expression of the T-cell activation marker Ox40 in NMO and multiple sclerosis lesions in different stages of activity. Results: All encephalitogenic T-cell lines used in our experiments induced brain inflammation with a comparable extent of blood brain barrier damage, allowing human NMO IgG to penetrate into the brain and spinal cord tissue. However, astrocyte destructive NMO lesions were only seen with T-cells, which showed signs of activation in the lesions. T-cell activation was reflected by the expression of the activation marker Ox40 and pronounced production of γ-IFN, which was able to increase the production of complement proteins and of the Fc gamma III receptor (Fcgr3) and decreased production of complement inhibitory protein Factor H in microglia. Conclusions: Our data indicate that local activation of T-cells provide an inflammatory environment in the CNS, which allows AQP4 auto-antibodies to induce astrocyte destructive NMO-like lesions