Low T-cell reactivity to TDP-43 peptides in ALS

• Verfasst von: Ramachandran, Swetha [VerfasserIn]
• Verfasst von: Grozdanov, Veselin D. [VerfasserIn]
• Verfasst von: Leins, Bianca [VerfasserIn]
• Verfasst von: Kandler, Katharina [VerfasserIn]
• Verfasst von: Witzel, Simon [VerfasserIn]
• Verfasst von: Medhanie Assmelash Mulaw [VerfasserIn]
• Verfasst von: Ludolph, Albert C. [VerfasserIn]
• Verfasst von: Weishaupt, Jochen H. [VerfasserIn]
• Verfasst von: Danzer, Karin M. [VerfasserIn]
• Titel: Low T-cell reactivity to TDP-43 peptides in ALS
• Verf.angabe: Swetha Ramachandran, Veselin Grozdanov, Bianca Leins, Katharina Kandler, Simon Witzel, Medhanie Mulaw, Albert C. Ludolph, Jochen H. Weishaupt and Karin M. Danzer
• E-Jahr: 2023
• Jahr: 21 July 2023
• Umfang: 10 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 08.11.2023
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2023
• Band/Heft Quelle: 14(2023), Artikel-ID 1193507, Seite 1-10
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2023.1193507
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1869692330

Abstract

BackgroundDysregulation of the immune system in amyotrophic lateral sclerosis (ALS) includes changes in T-cells composition and infiltration of T cells in the brain and spinal cord. Recent studies have shown that cytotoxic T cells can directly induce motor neuron death in a mouse model of ALS and that T cells from ALS patients are cytotoxic to iPSC-derived motor neurons from ALS patients. Furthermore, a clonal expansion to unknown epitope(s) was recently found in familial ALS and increased peripheral and intrathecal activation of cytotoxic CD8+ T cells in sporadic ALS.ResultsHere, we show an increased activation of peripheral T cells from patients with sporadic ALS by IL-2 treatment, suggesting an increase of antigen-experienced T cells in ALS blood. However, a putative antigen for T-cell activation in ALS has not yet been identified. Therefore, we investigated if peptides derived from TDP-43, a key protein in ALS pathogenesis, can act as epitopes for antigen-mediated activation of human T cells by ELISPOT and flow cytometry. We found that TDP-43 peptides induced only a weak MHCI or MHCII-restricted activation of both naïve and antigen-experienced T cells from healthy controls and ALS patients. Interestingly, we found less activation in T cells from ALS patients to TDP-43 and control stimuli. Furthermore, we found no change in the levels of naturally occurring auto-antibodies against full-length TDP-43 in ALS.ConclusionOur data suggests a general increase in antigen-experienced T cells in ALS blood, measured by in-vitro culture with IL-2 for 14 days. Furthermore, it suggests that TDP-43 is a weak autoantigen.