Twin study identifies early immunological and metabolic dysregulation of CD8 <sup>+</sup> T cells in multiple sclerosis
Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8<sup>+</sup> T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8<sup>+</sup> T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8<sup>+</sup> T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8<sup>+</sup> T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.
Authors
- Hanna Zimmermann (ORCID: https://orcid.org/0000-0002-1476-3477)
- Brigitte Wildemann (ORCID: https://orcid.org/0000-0002-5389-3338)
- Martin Kerschensteiner (ORCID: https://orcid.org/0000-0003-4898-9383)
- Birgit Ertl‐Wagner (ORCID: https://orcid.org/0000-0002-7896-7049)
- Tania Kümpfel (ORCID: https://orcid.org/0000-0001-7509-5268)
- Reinhard Hohlfeld (ORCID: https://orcid.org/0000-0002-6302-1488)
- Klaus Seelos
- Jürgen Haas (ORCID: https://orcid.org/0000-0002-2314-7465)
- Daniel Keeser (ORCID: https://orcid.org/0000-0002-0244-1024)
- Klaus Dornmair (ORCID: https://orcid.org/0000-0003-0342-5373)
- Lisa Ann Gerdes (ORCID: https://orcid.org/0000-0002-7053-3924)
- Andrea Flierl‐Hecht (ORCID: https://orcid.org/0000-0002-2359-1128)
- Thomas Korn (ORCID: https://orcid.org/0000-0002-3633-0955)
- Eduardo Beltrán (ORCID: https://orcid.org/0000-0002-7266-4098)
- Klara Eglseer
- Vladyslav Kavaka (ORCID: https://orcid.org/0009-0004-5837-3384)
- Clara de la Rosa del Val (ORCID: https://orcid.org/0000-0002-1344-0844)
- Matin Mortazavi (ORCID: https://orcid.org/0000-0002-0826-7661)
- Luisa Mutschler
- A.M. Martı́nez
Institutions
- University of Toronto (CA)
- Heidelberg University (DE)
- Hospital for Sick Children (CA)
- Munich Cluster for Systems Neurology (DE)
- SickKids Foundation (CA)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1126/sciimmunol.adj8094
- Citations
- 18
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 4.33