Abstract
T-cell receptor (TCR) repertoire diversity is a determining factor for the immune system capability in fighting infections and preventing autoimmunity. During life, the TCR repertoire diversity progressively declines as a physiological aging progress. The investigation of TCR repertoire dynamics over life represents a powerful tool unraveling the impact of immunosenescence in health and disease. 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. 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. Here we report an overview of current literature about the impact of immunosenescence and age-related TCR dynamics variation in autoimmunity, including MS.
Highlights
Immunosenescence is a natural consequence of the biological process of aging
These findings have been recently implemented by highthroughput sequencing (HTS): Jiang et al showed that Rheumatoid Arthritis (RA) patients share common features in their T-cell receptor (TCR) repertoire, e.g. clonal expansion in the effector memory T-cell compartment and in T helper 17 (Th17) cells, and TCR diversity has been correlated with RA disease activity [40]
Recent findings highlighted that the healthy TCR repertoire is strongly impacted by antigens encountered over lifetime and dwindles [3, 4, 10, 12], and such variations can be better appreciated in memory T cells after the age of 40 [4]; the shrinkage of TCR repertoire diversity correlates with the natural involution of the naïve T-cell compartment [4, 7, 13]
Summary
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]. Such changes reduce the immune system reactivity, making the individual more prone to infections and developing cancer. 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] In these circumstances memory T cells become prevalent, showing changes in either immunophenotype [5, 6] and gene expression [7, 8]. The composition of the memory T-cell compartment in advanced age is closely linked to the individual immunological history, e.g. the infections acquired during childhood and adolescence
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