Peripheral T cells from multiple sclerosis patients trigger synaptotoxic alterations in central neurons.
T cells
glutamate-excitotoxicity
multiple sclerosis
striatum
synaptic transmission
tumour necrosis factor
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
21
11
2018
accepted:
22
05
2019
pubmed:
28
5
2019
medline:
5
2
2021
entrez:
25
5
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Substances chimiques
Glutamic Acid
3KX376GY7L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
160-170Informations de copyright
© 2019 British Neuropathological Society.
Références
Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet 2018; 391: 1622-36
Calabrese M, Magliozzi R, Ciccarelli O, Geurts JJ, Reynolds R, Martin R. Exploring the origins of grey matter damage in multiple sclerosis. Nat Rev Neurosci 2015; 16: 147-58
Mandolesi G, Gentile A, Musella A, Fresegna D, De Vito F, Bullitta S, et al. Synaptopathy connects inflammation and neurodegeneration in multiple sclerosis. Nat Rev Neurol 2015; 11: 711-24
Lassmann H, Bradl M. Multiple sclerosis: experimental models and reality. Acta Neuropathol 2017; 133: 223-44
Centonze D, Muzio L, Rossi S, Cavasinni F, De Chiara V, Bergami A, et al. Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis. J Neurosci 2009; 29: 3442-52
Gentile A, Rossi S, Studer V, Motta C, De Chiara V, Musella A, et al. Glatiramer acetate protects against inflammatory synaptopathy in experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol 2013; 8: 651-63
Mandolesi G, Musella A, Gentile A, Grasselli G, Haji N, Sepman H, et al. Interleukin-1β alters glutamate transmission at purkinje cell synapses in a mouse model of multiple sclerosis. J Neurosci 2013; 33: 12105-21
Pitt D, Nagelmeier IE, Wilson HC, Raine CS. Glutamate uptake by oligodendrocytes: implications for excitotoxicity in multiple sclerosis. Neurology 2003; 61: 1113-20
Macrez R, Stys PK, Vivien D, Lipton SA, Docagne F. Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities. Lancet Neurol 2016; 15: 1089-102
Ling C, Verbny YI, Banks MI, Sandor M, Fabry Z. In situ activation of antigen-specific CD8+ T cells in the presence of antigen in organotypic brain slices. J Immunol 2008; 180: 8393-9
Göbel K, Bittner S, Cerina M, Herrmann AM, Wiendl H, Meuth SG. An ex vivo model of an oligodendrocyte-directed T-cell attack in acute brain slices. J Vis Exp 2015; 96: e52205. https://doi.org/10.3791/52205
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292-302
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444-52
Chiurchiù V, Leuti A, Saracini S, Fontana D, Finamore P, Giua R, et al. Resolution of inflammation is altered in chronic heart failure and entails a dysfunctional responsiveness of T lymphocytes. FASEB J 2019; 33: 909-16
Musella A, Fresegna D, Rizzo FR, Gentile A, Bullitta S, De Vito F, et al. A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum. Sci Rep 2017; 7: 7363
Damasceno A, Damasceno BP, Cendes F. Atrophy of reward-related striatal structures in fatigued MS patients is independent of physical disability. Mult Scler 2016; 22: 822-9
Calabrese M, Rinaldi F, Grossi P, Mattisi I, Bernardi V, Favaretto A, et al. Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in relapsing-remitting multiple sclerosis. Mult Scler 2010; 16: 1220-8
Tao G, Datta S, He R, Nelson F, Wolinsky JS, Narayana PA. Deep gray matter atrophy in multiple sclerosis: a tensor based morphometry. J Neurol Sci 2009; 282: 39-46
Rizzo FR, Musella A, De Vito F, Fresegna D, Bullitta S, Vanni V, et al. Tumor necrosis factor and interleukin-1β modulate synaptic plasticity during neuroinflammation. Neural Plast 2018; 14: 8430123
Santello M, Volterra A. TNFα in synaptic function: switching gears. Trends Neurosci 2012; 35: 638-47
Haji N, Mandolesi G, Gentile A, Sacchetti L, Fresegna D, Rossi S, et al. TNF-α-mediated anxiety in a mouse model of multiple sclerosis. Exp Neurol 2012; 237: 296-303
Filiano AJ, Gadani SP, Kipnis J. How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat Rev Neurosci 2017; 18: 375-84
Magliozzi R, Howell OW, Reeves C, Roncaroli F, Nicholas R, Serafini B, et al. Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010; 68: 477-93
Di Liberto G, Pantelyushin S, Kreutzfeldt M, Page N, Musardo S, Coras R, et al. Neurons under T cell attack coordinate phagocyte-mediated synaptic stripping. Cell 2018; 175: 458-71
Mori F, Nisticò R, Mandolesi G, Piccinin S, Mango D, Kusayanagi H, et al. Interleukin-1ß promotes long-term potentiation in patients with multiple sclerosis. Neuromolecular Med 2014; 16: 38-51
Mori F, Kusayanagi H, Nicoletti CG, Weiss S, Marciani MG, Centonze D. Cortical plasticity predicts recovery from relapse in multiple sclerosis. Mult Scler 2014; 20: 451-7
Nitsch R, Pohl EE, Smorodchenko A, Infante-Duarte C, Aktas O, Zipp F. Direct impact of T cells on neurons revealed by two-photon microscopy in living brain tissue. J Neurosci 2004; 24: 2458-64
Ellwardt E, Pramanik G, Luchtman D, Novkovic T, Jubal ER, Vogt J, et al. Maladaptive cortical hyperactivity upon recovery from experimental autoimmune encephalomyelitis. Nat Neurosci 2018; 21: 1392-403
Maimone D, Gregory S, Arnason BG, Reder AT. Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis. J Neuroimmunol 1991; 32: 67-74
Sharief MK, Hentges R. Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med 1991; 325: 467-72
Spuler S, Yousry T, Scheller A, Voltz R, Holler E, Hartmann M, et al. Multiple sclerosis: prospective analysis of TNF-alpha and 55 kDa TNF receptor in CSF and serum in correlation with clinical and MRI activity. J Neuroimmunol 1996; 66: 57-64
Magliozzi R, Howell O, Nicholas R, Cruciani C, Castellaro M, Romualdi C, et al. Inflammatory intrathecal profiles and cortical damage in multiple sclerosis. Ann Neurol 2018; 83: 739-55. https://doi.org/10.1002/ana.25197
Hu WT, Howell JC, Ozturk T, Gangishetti U, Kollhoff AL, Hatcher-Martin JM, et al. CSF Cytokines in Aging, Multiple Sclerosis, and Dementia. Front Immunol 2019; 15: 480
Shi N, Kawano Y, Matsuoka T, Mei F, Ishizu T, Ohyagi Y, et al. Increase of CD4+ TNFα+ IL-2-T cells in cerebrospinal fluid of multiple sclerosis patients. Mult Scler 2009; 15: 120-3