Autoreactive T cells target peripheral nerves in Guillain-Barré syndrome

Area of Science:

• Neuroimmunology
• Peripheral Nervous System Disorders
• Autoimmune Diseases

Background:

• Guillain-Barré syndrome (GBS) is a rare, heterogeneous autoimmune disorder causing progressive muscle weakness.
• The underlying mechanisms of GBS subtypes, particularly the role of T cells, are not fully understood.

Purpose of the Study:

• To investigate the role of autoreactive T cells in the pathophysiology of Guillain-Barré syndrome.
• To identify specific T cell populations and their targets in GBS patients with demyelinating variants.

Main Methods:

• In vitro T cell screening
• Single-cell RNA sequencing
• T cell receptor (TCR) sequencing
• Analysis of T cell clones from GBS patients and controls

Main Results:

• Identified autoreactive CD4+ T helper 1 (T_H1)-like and CD8+ T cells targeting peripheral nerve myelin antigens in GBS patients.
• Characterized over 1,000 autoreactive T cell clones, revealing a polyclonal TCR repertoire, specific CDR3β lengths, HLA-DR restrictions, and immunodominant epitopes.
• Found expanded autoreactive TCRβ clonotypes in GBS patients' blood and cerebrospinal fluid, shared across individuals but absent in controls.
• Detected myelin-reactive T cells in a nerve biopsy, directly linking them to disease.

Conclusions:

• Provided clear evidence of autoreactive T cell immunity in a subset of GBS patients.
• Opened new perspectives for understanding inflammatory peripheral neuropathies.
• Suggested potential for novel biomedical applications in GBS treatment.