AI Article Synopsis

  • * Investigation into TDP-43 peptides as potential antigenic triggers for T-cell activation revealed weak responses in both ALS patients and healthy controls.
  • * The findings imply that while there is a general increase in activated T cells in ALS, TDP-43 appears to function as a weak autoantigen, with no significant change in levels of auto-antibodies against it.

Article Abstract

Background: 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.

Results: 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.

Conclusion: Our data suggests a general increase in antigen-experienced T cells in ALS blood, measured by culture with IL-2 for 14 days. Furthermore, it suggests that TDP-43 is a weak autoantigen.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401033PMC
http://dx.doi.org/10.3389/fimmu.2023.1193507DOI Listing

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