T-cell-mediated regulation of neuroinflammation in neurodegenerative disorders. The scheme shows how the participation of inflammatory and anti-inflammatory subsets of encephalitogenic T-cells might regulate microglial fate and, consequently, the degeneration or survival of neurons. Whereas Th1, Th17, GM-CSF-producer CD4+ T-cells and γδT-cells favour the acquisition of the neurotoxic M1-like phenotype by microglia (left side of the illustration), Th2, Tregs and some kinds of CD8+ T-cells can contribute to the promotion of neurosupportive M2-like phenotype in microglial cells (right side of the illustration). The scheme in (a) shows the 'natural' scenario during the progression of multiple sclerosis (MS), Parkinson's disease (PD) and Alzheimer's disease (AD), which involve the M1-like microglia and consequent neurodegeneration; however, upon disease remission or immunosuppressive interventions, it is possible to induce the M2-like phenotype of microglia and neuroprotection. In the case of PD and AD, only Th1, Th17 and Tregs cells have been associated with the regulation of neuroinflammation. The role of other T-cell subsets in the regulation of neuroinflammation associated to AD and PD remains unexplored. The scheme in (b) illustrates the participation of T-cells in the regulation of neuroinflammation associated to amyotrophic lateral sclerosis (ALS). The physiopathological scenario of this disorder 'naturally' involves the participation of encephalitogenic or meningeal Tregs and Th2 cells, which strongly contribute to the induction of the anti-inflammatory M2-like phenotype on microglial cells, thus slowing the progression of the neurodegenerative process. BDNF, brain-derived neurotrophic factor; GDNF, glial cell-derived neurotrophic factor; IGF-1, insulin-like growth factor 1; RNS, reactive nitrogen species; ROS, reactive oxygen species.