T-cells from MS patients are toxic to mice neurons

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frodo
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T-cells from MS patients are toxic to mice neurons

Post by frodo » Tue May 28, 2019 6:15 am

This report points to something toxic in MS T-cells

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

https://onlinelibrary.wiley.com/doi/abs ... /nan.12569

Abstract

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 non‐active (na) relapsing remitting (RR) 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 of 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.

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