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

Area of Science:

• Neuroimmunology
• Cellular Neuroscience

Background:

• Multiple sclerosis (MS) involves T cell infiltration into the brain, contributing to neuroinflammation and neuronal damage.
• T cells and microglia in experimental autoimmune encephalomyelitis (EAE) models enhance glutamatergic transmission, leading to excitotoxicity in MS and EAE brains.

Purpose of the Study:

• To investigate the synaptic role of T cells isolated from multiple sclerosis (MS) patients.
• To determine if T cells from MS patients influence glutamatergic transmission in central neurons.

Main Methods:

• A chimeric model combining human T cells and murine brain slices was used.
• Patch clamp electrophysiology recorded glutamatergic transmission in the presence of T cells from healthy subjects (HS) and MS patients (active and non-active).
• Tumor necrosis factor (TNF) expression in T cells was assessed via intracellular staining and flow cytometry.

Main Results:

• T cells from active MS patients significantly increased glutamatergic transmission kinetics in striatal neurons compared to HS and non-active MS patients.
• This enhancement of glutamatergic transmission was blocked by etanercept, a TNF receptor antagonist.
• T cells from active MS patients exhibited higher TNF expression than those from non-active MS patients and HS subjects.

Conclusions:

• T cells from MS patients possess synaptotoxic potential.
• Infiltrating T cells during MS inflammation may modulate neuronal activity via TNF-mediated mechanisms.
• This contributes to glutamate excitotoxicity in central neurons, highlighting a potential therapeutic target.