Protective and Regenerative Roles of T Cells in Central Nervous System Disorders

Abstract

Pathogenic mechanisms of T cells in several central nervous system (CNS) disorders are well-established. However, more recent studies have uncovered compelling beneficial roles of T cells in neurological diseases, ranging from tissue protection to regeneration. These divergent functions arise due to the diversity of T cell subsets, particularly CD4+ T cells. Here, we review the beneficial impact of T cell subsets in a range of neuroinflammatory and neurodegenerative diseases including multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and CNS trauma. Both T cell-secreted mediators and direct cell contact-dependent mechanisms deliver neuroprotective, neuroregenerative and immunomodulatory signals in these settings. Understanding the molecular details of these beneficial T cell mechanisms will provide novel targets for therapeutic exploitation that can be applied to a range of neurological disorders.

CD45RA, CD8β, and IFNγ Are Potential Immune Biomarkers of Human Cognitive Function

“…During the last years there has been a change of dogma whereby T cells are also endowed with properties that promote behavioral improvement, brain plasticity and cognition (4,(38)(39)(40)(41). Indeed, recent studies in clinical and experimental neurodegenerative settings have provided important insights into the neuroprotective role of T cells (42)(43)(44).…”

“…However, the accumulated evidence from clinical and experimental studies has consolidated the view that the innate and adaptive Abbreviations: TEMRA, effector-memory CD45RA+ T cells; CMV, cytomegalovirus; GDS, global deterioration scale; NCI, no cognitive impairment; MCI, mild cognitive impairment; CI, cognitive impairment. components of the immunological system are crucial players in neuronal homeostasis and cognitive function by fine-tuning the balance between neuroprotection and neurodegeneration (2)(3)(4). Thus, early studies in mice showed that CD4+ and CD8+ T cell deficiency was associated with cognitive dysfunction and deficient remyelination after spinal-cord injury, and that thymus-derived CD4+CD25+ Treg cells specific for myelin self-antigens were necessary to confer protection after injury to the CNS (5)(6)(7).…”

The Role of the Blood Neutrophil-to-Lymphocyte Ratio in Aneurysmal Subarachnoid Hemorrhage

“…Lymphocytes are found in the CNS after aSAH and are mainly involved in the protective mechanism against brain injury ( 57 ). Tregs play a key role in the elimination of inflammation and are the main brain-protective immunomodulator ( 58 , 59 ). Tregs can reduce the inflammatory response by blocking the activation of the TLR4/nuclear factor-kappa B (NF-κB) signaling pathway, inducing the transformation of microglia toward a more favorable M2-like phenotype inhibiting the effect of neutrophil-derived MMP-9 to protect the integrity of the BBB and EC function ( 60 , 61 ).…”

Lesion stage-dependent causes for impaired remyelination in MS

“…In animal experiments, proliferation and migration of oligodendrocyte precursor cells (OPC) as well as their differentiation into mature myelinating oligodendrocytes is required for successful remyelination. These complex processes are regulated by the interaction of OPC and oligodendrocytes with neurons and axons, astrocytes as well as immune cells, such as macrophages/microglia, T cells, and B cells (for review see [24,25,27,42]). In progressive MS, OPC are still present in MS lesions albeit in reduced numbers and unevenly distributed, whereas mature oligodendrocytes are almost completely lacking [11,39,69].…”