T cells in amyotrophic lateral sclerosis.
The inflammatory process in ALS involves infiltration of T cells and activation of antigen presenting cells co-localizing with motor neuron damage in the brain and spinal cord. The role of T cells in the pathogenic process is not settled. T cells may damage motor neurons by cell-cell contact or cytokine secretion, or contribute indirectly to motor neuron damage through activation of microglia and macrophages. Alternatively, T cell infiltration may be an epiphenomenon related to clearance of dead motor neurons. Lessons from animal models of neuroinflammation and neurodegeneration have shown that T cell responses can be neuroprotective or even enhance neurogenesis. Therefore, it is possible that T cells can be induced to slow motor neuron destruction and facilitate repair in ALS. The T cell modulating drug glatiramer acetate has shown promising results in animal models, and is being currently investigated in a phase II trial in ALS. This paper reviews the evidence for T cells as pathogenic players and therapeutic targets in ALS.
Holmøy
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Department of Neurology, Institute of Immunology, University of Oslo, Ullevål University Hospital, Oslo, Norway. trygve.holmoy@medisin.uio.no
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate