Persistent and compartmentalized T cell immunity in ALS.

Long-lived intrathecal T cell clonotypes in ALS CSF show immunological synapse-like antigen-presenting cell–T cell complexes, supporting intrathecal antigen presentation.

• Why it matters: Mechanisms linking T cell activation to ALS progression are unclear, especially how immune responses differ between the CNS compartment and the circulation.
• What they did: Using single-cell RNA and T cell receptor sequencing, longitudinal immune profiling, and imaging flow cytometry, the study identified intrathecal clonotypes and antigen-presenting cell–T cell complexes.
• The result: Higher CSF CD4 effector, CD4 regulatory, and CD8 T cell frequencies were associated with slower progression, while circulating CD4 effector and regulatory T cells and CSF cytomegalovirus-specific T cells (with anticytomegalovirus serum antibodies) were associated with faster progression and shorter survival in sporadic ALS.