![]() ![]() MS is widely considered an autoimmune disease, however the antigen that triggers the abnormal immune response is still unknown. Multiple Sclerosis (MS) is an inflammatory, systemic, heterogeneous disease in which autoreactive T cells migrate from the periphery to the central nervous system (CNS), leading to myelin disruption. This is particularly crucial in autoimmune disorders, in which the disruption of immune tolerance and immune aging are mutually related, as it has been observed in patients with Rheumatoid Arthritis (RA), who showed a disease-dependent premature and accelerated immunosenescence process ( 15). hampering to repair tissue damage and to heal from acute infections) and contributing to disease progression ( 14). Albeit this process naturally occurs in both health and disease, in the latter case it may exacerbate the pathological condition, weakening immune defense and capability of recovering (e.g. The application of high-throughput sequencing (HTS) demonstrated that age-dependent T-cell compartment depletion reflects the impairment of the T-cell receptor (TCR) repertoire diversity that appears reduced, leading to a narrowed antigen recognition potential breadth ( 4, 9, 13). Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are two examples of pathogens that infect a massive part of the human population (global prevalence is up to 80% and 95% for CMV and EBV, respectively) ( 11, 12), leaving a signature within the immune system that is common to most of individuals and that, in some cases, alters the immune system composition as age progresses. Viruses that infect the organism and then become lifelong latent have a major role in shaping the T-cell response and building-up the memory T-cell repertoire ( 9, 10). the infections acquired during childhood and adolescence. The composition of the memory T-cell compartment in advanced age is closely linked to the individual immunological history, e.g. In these circumstances memory T cells become prevalent, showing changes in either immunophenotype ( 5, 6) and gene expression ( 7, 8). Over time, the T-cell compartment gradually switches towards a homeostatic maintenance of the existing cells rather than generating new ones, as reflected by the reduction of naïve cells ( 3, 4). T lymphocytes are profoundly impacted by immune aging. Such changes reduce the immune system reactivity, making the individual more prone to infections and developing cancer. The immune system progressively declines throughout life: the involution of thymic activity begins with puberty and, as age advances, the regenerative potential of immune cells decreases, skewing the T- and B-cell compartment ( 1, 2). Immunosenescence is a natural consequence of the biological process of aging. Here we report an overview of current literature about the impact of immunosenescence and age-related TCR dynamics variation in autoimmunity, including MS. ![]() Crossing knowledge on the TCR repertoire dynamics over MS patients’ life is fundamental to investigate disease mechanisms, and the advent of high- throughput sequencing (HTS) has significantly increased our knowledge on the topic. Multiple Sclerosis (MS) is a demyelinating, inflammatory, T-cell mediated autoimmune disease of the Central Nervous System in which age is crucial: it is the most widespread neurological disease among young adults and, furthermore, patients age may impact on MS progression and treatments outcome. The investigation of TCR repertoire dynamics over life represents a powerful tool unraveling the impact of immunosenescence in health and disease. During life, the TCR repertoire diversity progressively declines as a physiological aging progress. T-cell receptor (TCR) repertoire diversity is a determining factor for the immune system capability in fighting infections and preventing autoimmunity.
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