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| 001 | 259703 | ||
| 005 | 20240112171422.0 | ||
| 024 | 7 | _ | |a pmc:PMC10401033 |2 pmc |
| 024 | 7 | _ | |a 10.3389/fimmu.2023.1193507 |2 doi |
| 024 | 7 | _ | |a altmetric:151821625 |2 altmetric |
| 024 | 7 | _ | |a pmid:37545536 |2 pmid |
| 037 | _ | _ | |a DZNE-2023-00775 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Ramachandran, Swetha |b 0 |
| 245 | _ | _ | |a Low T-cell reactivity to TDP-43 peptides in ALS |
| 260 | _ | _ | |a Lausanne |c 2023 |b Frontiers Media |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1692950741_28578 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Dysregulation 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.Here, 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.Our 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. |
| 536 | _ | _ | |a 352 - Disease Mechanisms (POF4-352) |0 G:(DE-HGF)POF4-352 |c POF4-352 |f POF IV |x 0 |
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| 588 | _ | _ | |a Dataset connected to CrossRef, Journals: pub.dzne.de |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Amyotrophic Lateral Sclerosis: metabolism |2 MeSH |
| 650 | _ | 2 | |a CD8-Positive T-Lymphocytes: metabolism |2 MeSH |
| 650 | _ | 2 | |a DNA-Binding Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Interleukin-2 |2 MeSH |
| 650 | _ | 7 | |a DNA-Binding Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a T cells |2 Other |
| 650 | _ | 7 | |a TDP-43 |2 Other |
| 650 | _ | 7 | |a amyotrophic lateral sclerosis |2 Other |
| 650 | _ | 7 | |a autoantibody |2 Other |
| 650 | _ | 7 | |a autoantigen |2 Other |
| 650 | _ | 7 | |a Interleukin-2 |2 NLM Chemicals |
| 650 | _ | 7 | |a TARDBP protein, human |2 NLM Chemicals |
| 700 | 1 | _ | |a Grozdanov, Veselin |0 P:(DE-2719)9001519 |b 1 |u dzne |
| 700 | 1 | _ | |a Leins, Bianca |b 2 |
| 700 | 1 | _ | |a Kandler, Katharina |b 3 |
| 700 | 1 | _ | |a Witzel, Simon |b 4 |
| 700 | 1 | _ | |a Mulaw, Medhanie |b 5 |
| 700 | 1 | _ | |a Ludolph, Albert C. |0 P:(DE-2719)2812633 |b 6 |u dzne |
| 700 | 1 | _ | |a Weishaupt, Jochen H. |b 7 |
| 700 | 1 | _ | |a Danzer, Karin M. |0 P:(DE-2719)9001513 |b 8 |e Last author |u dzne |
| 773 | _ | _ | |a 10.3389/fimmu.2023.1193507 |g Vol. 14, p. 1193507 |0 PERI:(DE-600)2606827-8 |p 1193507 |t Frontiers in immunology |v 14 |y 2023 |x 1664-3224 |
| 856 | 4 | _ | |y OpenAccess |u https://pub.dzne.de/record/259703/files/DZNE-2023-00775.pdf |
| 856 | 4 | _ | |y OpenAccess |u https://pub.dzne.de/record/259703/files/DZNE-2023-00775_SUPP1.PDF |
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