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.
Highlights
The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Belfast, United Kingdom
One approach to study the role of the adaptive immune system in Traumatic brain injury (TBI) used the controlled cortical impact (CCI) model of TBI in mice in which air or an electromagnetic-driven piston is used to penetrate the brain at a known distance and velocity [103, 105]
Low levels of adaptive immune cell infiltration occur in central nervous system (CNS) homeostasis, this is increased across neurological disorders
Summary
The adaptive immune system is made up of B (for bone marrow-derived) and T (for thymus-derived) lymphocytes, that have evolved to protect us from pathogens and mount a faster immune response for repeat infections against the same pathogen [1]. Naïve CD4+ T lymphocytes undergo differentiation into various subsets, specification of which can be influenced by expression of cytokines in the microenvironment as well as intracellular transcription factors [2]. This review will focus on CD4+ T lymphocytes, and to a lesser degree, CD8+ T lymphocytes, and emerging regenerative roles of these cells in neurological disease. Subset functional roles and characterization are reviewed in more detail in Caza and Landas [3]
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