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.