Aims The crucial step in the pathogenic events that lead to the development and the progression of multiple sclerosis (MS) is the infiltration of autoreactive T cells in the brain. Data from experimental autoimmune encephalomyelitis (EAE) mice indicate that, together with microglia, T cells are responsible for the enhancement of the glutamatergic transmission in central neurons, contributing to glutamate-mediated excitotoxicity, a pathological hallmark of both EAE and MS brains. Here, we addressed the synaptic role of T cells taken from MS patients.Methods A chimeric model of human T cells and murine brain slices was established to record, by Patch Clamp technique, the glutamatergic transmission in the presence of T cells isolated from the peripheral blood of healthy subjects (HS), active (a) and nonactive (na) relapsing remitting MS patients. Intracellular staining and flow cytometry were used to assess tumour necrosis factor (TNF) expression in T cells.Results Chimeric experiments indicated that, compared to HS and naMS, T cells from aMS induced an increase in glutamatergic kinetic properties of striatal neurons. Such alteration, reminiscent of the those induced by EAE T cells, was blocked by incubation of the slices with etanercept, a TNF receptor antagonist. Of note, T cells from aMS expressed more TNF than naMS patients and HS subjects.Conclusion These data highlight the synaptotoxic potential retained by MS T cells, suggesting that during the inflammatory phase of the disease infiltrating T cells could influence the neuronal activity contributing to the TNF-mediated mechanisms of glutamate excitotoxicity in central neurons.

Gentile, A., De Vito, F., Fresegna, D., Rizzo, F.r., Bullitta, S., Guadalupi, L., et al. (2020). Peripheral T cells from multiple sclerosis patients trigger synaptotoxic alterations in central neurons. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 46(2), 160-170 [10.1111/nan.12569].

Peripheral T cells from multiple sclerosis patients trigger synaptotoxic alterations in central neurons

Gentile, A;Fresegna, D;Rizzo, F R;Bullitta, S;Vanni, V;Buttari, F;Marfia, G A;Centonze, D;Musella, A
2020-02-01

Abstract

Aims The crucial step in the pathogenic events that lead to the development and the progression of multiple sclerosis (MS) is the infiltration of autoreactive T cells in the brain. Data from experimental autoimmune encephalomyelitis (EAE) mice indicate that, together with microglia, T cells are responsible for the enhancement of the glutamatergic transmission in central neurons, contributing to glutamate-mediated excitotoxicity, a pathological hallmark of both EAE and MS brains. Here, we addressed the synaptic role of T cells taken from MS patients.Methods A chimeric model of human T cells and murine brain slices was established to record, by Patch Clamp technique, the glutamatergic transmission in the presence of T cells isolated from the peripheral blood of healthy subjects (HS), active (a) and nonactive (na) relapsing remitting MS patients. Intracellular staining and flow cytometry were used to assess tumour necrosis factor (TNF) expression in T cells.Results Chimeric experiments indicated that, compared to HS and naMS, T cells from aMS induced an increase in glutamatergic kinetic properties of striatal neurons. Such alteration, reminiscent of the those induced by EAE T cells, was blocked by incubation of the slices with etanercept, a TNF receptor antagonist. Of note, T cells from aMS expressed more TNF than naMS patients and HS subjects.Conclusion These data highlight the synaptotoxic potential retained by MS T cells, suggesting that during the inflammatory phase of the disease infiltrating T cells could influence the neuronal activity contributing to the TNF-mediated mechanisms of glutamate excitotoxicity in central neurons.
feb-2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
T cells
glutamate-excitotoxicity
multiple sclerosis
striatum
synaptic transmission
tumour necrosis factor
Gentile, A., De Vito, F., Fresegna, D., Rizzo, F.r., Bullitta, S., Guadalupi, L., et al. (2020). Peripheral T cells from multiple sclerosis patients trigger synaptotoxic alterations in central neurons. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 46(2), 160-170 [10.1111/nan.12569].
Gentile, A; De Vito, F; Fresegna, D; Rizzo, Fr; Bullitta, S; Guadalupi, L; Vanni, V; Buttari, F; Stampanoni Bassi, M; Leuti, A; Chiurchiù, V; Marfia, Ga; Mandolesi, G; Centonze, D; Musella, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/257252
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