Low T-cell reactivity to TDP-43 peptides in ALS
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 th...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
21 July 2023
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| In: |
Frontiers in immunology
Year: 2023, Volume: 14, Pages: 1-10 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2023.1193507 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2023.1193507 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1193507 
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| Author Notes: | Swetha Ramachandran, Veselin Grozdanov, Bianca Leins, Katharina Kandler, Simon Witzel, Medhanie Mulaw, Albert C. Ludolph, Jochen H. Weishaupt and Karin M. Danzer |
| Summary: | 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. |
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| Item Description: | Gesehen am 08.11.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2023.1193507 |