Expanding Role of T Cells in Human Autoimmune Diseases of the Central Nervous System

Abstract

It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease. Aberrant T cell responses, in particular, are key in driving autoimmunity and have been traditionally associated with multiple sclerosis. Yet, it is evident that there are other neurological diseases in which autoreactive T cells have an active role in pathogenesis. In this review, we report on the recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS) autoimmune disorders that are currently postulated to be primarily T cell driven. We also explore the autoreactive T cell response in a recently emerging group of syndromes characterized by autoantibodies against neuronal cell-surface proteins. Common methodology implemented in T cell biology is further considered as it is an important determinant in their detection and characterization. An improved understanding of the contribution of autoreactive T cells expands our knowledge of the autoimmune response in CNS disorders and can offer novel methods of therapeutic intervention.

Insights into the Role of Neuroinflammation in the Pathogenesis of Multiple Sclerosis

“…MS is considered the leading cause of non-traumatic disability in adults. Even though many people with MS will suffer a limited degree of disability, about 60% of MS sufferers may be wheelchair bound or will require mobility assistance within 20-25 years after onset [2,10,11]. This has major implications for the quality of life of afflicted people, their social network, and for the cost to society if their condition is not adequately managed.…”

“…For some people, MS is characterised by periods of relapse and remission while, for others, the disease exhibits a progressive pattern. Due to the spectrum of symptoms and clinical manifestations, it is not surprising that the life of MS patients may become unpredictable [4,8,[11][12][13].…”

“…However, it is quite well-accepted that there are multiple risk factors contributing to the disease, including genetic predisposition, and non-genetic triggers, such as prior exposure to viral infections, changes in metabolism, or environmental factors, together potentially initiating a myelin-specific T-cell self-reactive autoimmune response that leads to the pathological presentation of the disease [11,14].…”

“…It is believed that the link with MS is related to the role these MHCs play in auto-antigen presentation to the adaptive immune system as it triggers the auto-reactivity component of the disease, but the process is not clearly elucidated [8,11,16,17].…”

“…These studies attributed the findings to the level of exposure to sun light and vitamin D intake through diet, demonstrating a clear association between vitamin D-deficiency and risk of MS development [15,[23][24][25]. Many of these studies suggested that lower serum vitamin D levels could be predictive of higher incidence of relapses among MS patients [11,[26][27][28].…”