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Acta Neuropathol Commun. 2013 Dec 24;1:85. doi: 10.1186/2051-5960-1-85.

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

Author information

1
Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, Vienna A-1090, Austria. monika.bradl@meduniwien.ac.at.

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.

PMID:
24367907
PMCID:
PMC3879999
DOI:
10.1186/2051-5960-1-85
[Indexed for MEDLINE]
Free PMC Article
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