Autoreactive T cells target peripheral nerves in Guillain-Barré syndrome

Nature. 2024 Feb;626(7997):160-168. doi: 10.1038/s41586-023-06916-6. Epub 2024 Jan 17.


Guillain-Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3β lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRβ clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.

MeSH terms

  • Autoimmunity*
  • Biopsy
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / pathology
  • Guillain-Barre Syndrome* / blood
  • Guillain-Barre Syndrome* / cerebrospinal fluid
  • Guillain-Barre Syndrome* / etiology
  • Guillain-Barre Syndrome* / immunology
  • HLA-DR Antigens / immunology
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunologic Memory
  • Myelin Sheath / immunology
  • Peripheral Nerves* / immunology
  • Peripheral Nerves* / pathology
  • Peripheral Nervous System Diseases* / complications
  • Peripheral Nervous System Diseases* / immunology
  • Peripheral Nervous System Diseases* / pathology
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • Th1 Cells* / immunology
  • Th1 Cells* / pathology


  • HLA-DR Antigens
  • Immunodominant Epitopes
  • Receptors, Antigen, T-Cell