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000259703 1001_ $$aRamachandran, Swetha$$b0
000259703 245__ $$aLow T-cell reactivity to TDP-43 peptides in ALS
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000259703 520__ $$aDysregulation 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.
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000259703 650_2 $$2MeSH$$aHumans
000259703 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: metabolism
000259703 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: metabolism
000259703 650_2 $$2MeSH$$aDNA-Binding Proteins: metabolism
000259703 650_2 $$2MeSH$$aInterleukin-2
000259703 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000259703 650_7 $$2Other$$aT cells
000259703 650_7 $$2Other$$aTDP-43
000259703 650_7 $$2Other$$aamyotrophic lateral sclerosis
000259703 650_7 $$2Other$$aautoantibody
000259703 650_7 $$2Other$$aautoantigen
000259703 650_7 $$2NLM Chemicals$$aInterleukin-2
000259703 650_7 $$2NLM Chemicals$$aTARDBP protein, human
000259703 7001_ $$0P:(DE-2719)9001519$$aGrozdanov, Veselin$$b1$$udzne
000259703 7001_ $$aLeins, Bianca$$b2
000259703 7001_ $$aKandler, Katharina$$b3
000259703 7001_ $$aWitzel, Simon$$b4
000259703 7001_ $$aMulaw, Medhanie$$b5
000259703 7001_ $$0P:(DE-2719)2812633$$aLudolph, Albert C.$$b6$$udzne
000259703 7001_ $$aWeishaupt, Jochen H.$$b7
000259703 7001_ $$0P:(DE-2719)9001513$$aDanzer, Karin M.$$b8$$eLast author$$udzne
000259703 773__ $$0PERI:(DE-600)2606827-8$$a10.3389/fimmu.2023.1193507$$gVol. 14, p. 1193507$$p1193507$$tFrontiers in immunology$$v14$$x1664-3224$$y2023
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