ORIGINAL RESEARCH article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1604452
T Cell Repertoire Correlates with Cytokine Imbalance in Multiple Sclerosis Patients
Provisionally accepted
Lisa Weidner1,2*
Rodolphe Poupardin3
Tobias Zrzavy4
Sandra Laner-Plamberger2Georg Gratz1
Tanja Eichhorn5
Viktoria Weber5
Paulus Stefan Rommer4
Christof Jungbauer1,2
Dirk Strunk1,3- 1Blood Service for Vienna, Lower Austria and Burgenland, Austrian Red Cross, Wien, Austria
- 2Paracelsus Medical University (PMU), Department of Transfusion Medicine, University Hospital Salzburg, Salzburg, Salzburg, Austria
- 3Cell Therapy Institute, Paracelsus Medical University, Salzburg, Austria, Salzburg, Austria
- 4Department of Neurology, Medical University of Vienna, Vienna, Vienna, Austria
- 5Center for Biomedical Technology, Department for Biomedical Research, Danube University Krems, Krems, Austria
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Background and Objective: Multiple sclerosis (MS) is mediated by innate and adaptive immune response deviation involving immune cells and cytokines. Here, we investigated whether combined cytokine profiling and T cell receptor (TCR) repertoire analysis can better display the complex landscape of MS-driving immune responses.Methods: We used advanced computational methods to systematically cluster highly variable individual levels of 48 cytokines in cerebrospinal fluid (CSF) and blood of 24 MS patients compared to nine controls. Relevant TCR sequences were compared to 88 healthy controls. We correlated cytokines with predominant shared TCR sequences to identify immune response networks.Results: MS patients had significantly elevated MIP-1a and IP-10 levels in CSF, and additional 36 blood cytokines variably but significantly elevated. We identified 77 predominantly pro-inflammatory cytokine correlations in MS-CSF. TCR sequencing revealed more productive rearrangements in CSF of MS and a significantly higher shared clone recovery rate in blood. We found significant associations involving 492 unique sequences and 34 cytokines in blood. Particularly the less significant individual cytokine deviations were found to contribute to a general Th1-biased type I immune response correlating with clonal expansion of T cells directed against EBV, CMV and other infectious agents.Conclusion: Correlation of significantly altered T cell repertoire with cytokine deviations in MS despite individual patient data variability indicating that future diagnostic strategies may need to address immune response patterns rather than individual protein targets.
Keywords: Neuroscience, Multiple Sclerosis, T cell repertoire, Cytokine imbalance, bioinformatics
Received: 02 Apr 2025; Accepted: 03 Jun 2025.
Copyright: © 2025 Weidner, Poupardin, Zrzavy, Laner-Plamberger, Gratz, Eichhorn, Weber, Rommer, Jungbauer and Strunk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lisa Weidner, Blood Service for Vienna, Lower Austria and Burgenland, Austrian Red Cross, Wien, Austria
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