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Neuromyelitis optica, T cell activation, Aquaporin 4, Lesion, IFN-γ
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
