%0 Journal Article
%A Ramachandran, Swetha
%A Grozdanov, Veselin
%A Leins, Bianca
%A Kandler, Katharina
%A Witzel, Simon
%A Mulaw, Medhanie
%A Ludolph, Albert C.
%A Weishaupt, Jochen H.
%A Danzer, Karin M.
%T Low T-cell reactivity to TDP-43 peptides in ALS
%J Frontiers in immunology
%V 14
%@ 1664-3224
%C Lausanne
%I Frontiers Media
%M DZNE-2023-00775
%P 1193507
%D 2023
%X 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.
%K Humans
%K Amyotrophic Lateral Sclerosis: metabolism
%K CD8-Positive T-Lymphocytes: metabolism
%K DNA-Binding Proteins: metabolism
%K Interleukin-2
%K DNA-Binding Proteins (NLM Chemicals)
%K T cells (Other)
%K TDP-43 (Other)
%K amyotrophic lateral sclerosis (Other)
%K autoantibody (Other)
%K autoantigen (Other)
%K Interleukin-2 (NLM Chemicals)
%K TARDBP protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC10401033
%$ pmid:37545536
%R 10.3389/fimmu.2023.1193507
%U https://pub.dzne.de/record/259703