Back to Search
Start Over
T cell-activation in neuromyelitis optica lesions plays a role in their formation.
- Source :
-
Acta neuropathologica communications [Acta Neuropathol Commun] 2013 Dec 24; Vol. 1, pp. 85. Date of Electronic Publication: 2013 Dec 24. - Publication Year :
- 2013
-
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.<br />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.<br />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.
- Subjects :
- Animals
Aquaporin 4 metabolism
Astrocytes immunology
Astrocytes pathology
Brain pathology
Cell Line
Cells, Cultured
Encephalomyelitis, Autoimmune, Experimental immunology
Encephalomyelitis, Autoimmune, Experimental pathology
Immunoglobulin G metabolism
Interferon-gamma metabolism
Macrophages immunology
Macrophages pathology
Microglia pathology
Microglia physiology
Multiple Sclerosis immunology
Multiple Sclerosis pathology
Neuromyelitis Optica pathology
Rats, Inbred Lew
Receptors, IgG metabolism
Spinal Cord pathology
T-Lymphocytes pathology
Brain immunology
Neuromyelitis Optica immunology
Spinal Cord immunology
T-Lymphocytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2051-5960
- Volume :
- 1
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica communications
- Publication Type :
- Academic Journal
- Accession number :
- 24367907
- Full Text :
- https://doi.org/10.1186/2051-5960-1-85