Highly encephalitogenic aquaporin 4-specific T cells and NMO-IgG jointly orchestrate lesion location and tissue damage in the CNS

Abstract In neuromyelitis optica (NMO), astrocytes become targets for pathogenic aquaporin 4 (AQP4)-specific antibodies which gain access to the central nervous system (CNS) in the course of inflammatory processes. Since these antibodies belong to a T cell-dependent subgroup of immunoglobulins, and since NMO lesions contain activated CD4+ T cells, the question arose whether AQP4-specific T cells might not only provide T cell help for antibody production, but also play an important role in the induction of NMO lesions. We show here that highly pathogenic, AQP4-peptide-specific T cells exist in Lewis rats, which recognize AQP4268–285 as their specific antigen and cause severe panencephalitis. These T cells are re-activated behind the blood–brain barrier and deeply infiltrate the CNS parenchyma of the optic nerves, the brain, and the spinal cord, while T cells with other AQP4-peptide specificities are essentially confined to the meninges. Although AQP4268–285-specific T cells are found throughout the entire neuraxis, they have NMO-typical “hotspots” for infiltration, i.e. periventricular and periaqueductal regions, hypothalamus, medulla, the dorsal horns of spinal cord, and the optic nerves. Most remarkably, together with NMO-IgG, they initiate large astrocyte-destructive lesions which are located predominantly in spinal cord gray matter. We conclude that the processing of AQP4 by antigen presenting cells in Lewis rats produces a highly enc...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Source: Health Physics - Category: Physics Authors: Tags: Am J Phys Med Rehabil Source Type: research
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Source: Best Practice and Research Clinical Anaesthesiology - Category: Anesthesiology Source Type: research
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Source: Brazilian Journal of Anesthesiology - Category: Anesthesiology Source Type: research
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Source: International Reviews of Immunology - Category: Allergy & Immunology Tags: Int Rev Immunol Source Type: research
Date: Monday, 10 21, 2019; Speaker: See attached agenda; Building 10; Masur (10/21/19) and Lipsett (10/22/19)
Source: NIH Calendar of Events - Category: American Health Source Type: events
Date: Wednesday, 10 23, 2019; Speaker: Joseph Zaia, Ph. D., Boston University; Building 50; 1227/1233; Videocast Event
Source: NIH Calendar of Events - Category: American Health Source Type: events
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Source: NIH Calendar of Events - Category: American Health Source Type: events
Date: Thursday, 10 24, 2019; Speaker: Joachim Lingner, Ph.D., Full Professor for Life Sciences, EPF Lausanne (Swiss Federal Institute of Technology); Building: Building 37; Conference Room 6041/6107
Source: NIH Calendar of Events - Category: American Health Source Type: events
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Source: NIH Calendar of Events - Category: American Health Source Type: events
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