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@ARTICLE{Ramachandran:259703,
      author       = {Ramachandran, Swetha and Grozdanov, Veselin and Leins,
                      Bianca and Kandler, Katharina and Witzel, Simon and Mulaw,
                      Medhanie and Ludolph, Albert C. and Weishaupt, Jochen H. and
                      Danzer, Karin M.},
      title        = {{L}ow {T}-cell reactivity to {TDP}-43 peptides in {ALS}},
      journal      = {Frontiers in immunology},
      volume       = {14},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DZNE-2023-00775},
      pages        = {1193507},
      year         = {2023},
      abstract     = {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.},
      keywords     = {Humans / Amyotrophic Lateral Sclerosis: metabolism /
                      CD8-Positive T-Lymphocytes: metabolism / DNA-Binding
                      Proteins: metabolism / Interleukin-2 / DNA-Binding Proteins
                      (NLM Chemicals) / T cells (Other) / TDP-43 (Other) /
                      amyotrophic lateral sclerosis (Other) / autoantibody (Other)
                      / autoantigen (Other) / Interleukin-2 (NLM Chemicals) /
                      TARDBP protein, human (NLM Chemicals)},
      cin          = {AG Danzer / Clinical Study Center Ulm},
      ddc          = {610},
      cid          = {I:(DE-2719)5000072 / I:(DE-2719)5000077},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC10401033},
      pubmed       = {pmid:37545536},
      doi          = {10.3389/fimmu.2023.1193507},
      url          = {https://pub.dzne.de/record/259703},
}