T cell senescence and cardiovascular diseases

Abstract

Age-related changes in the immune system, commonly termed "immunosenescence," contribute to deterioration of the immune response and fundamentally impact the health and survival of elderly individuals. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. Senescent T cells have the ability to produce large quantities of proinflammatory cytokines and cytotoxic mediators; thus, they have been implicated in the pathogenesis of many chronic inflammatory diseases. Recently, an increasing body of evidence has suggested that senescent T cells also have pathogenic potential in cardiovascular diseases, such as hypertension, atherosclerosis, and myocardial infarction, underscoring the detrimental roles of these cells in various chronic inflammatory responses. Given that cardiovascular disease is the number one cause of death worldwide, there is great interest in understanding the contribution of age-related immunological changes to its pathogenesis. In this review, we discuss general features of age-related alterations in T cell immunity and the possible roles of senescent T cells in the pathogenesis of cardiovascular disease.

Unusual CD4+CD28−T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders

“…Of interest, chronic exposure to TNF-α leads to downregulation of the CD28-specific initiator complex and consequently results in decreased CD28 expression in CD4 + T cells at the transcriptional level (202223). Furthermore, repeated antigenic stimulation leads to chronic inflammation, making proinflammatory cytokines such as TNF-α abundant and therefore, loss of CD28 due to both replicative senescence and cytokine exposure may not be mutually exclusive in inflammatory disorders (10). Moreover, increased TNF-α is one of the features of inflammaging, which is a low-grade, chronic, systemic pro-inflammatory state frequently observed in the elderly that is associated with the unexpected upregulation of proinflammatory responses later in life (10242526).…”

“…Furthermore, repeated antigenic stimulation leads to chronic inflammation, making proinflammatory cytokines such as TNF-α abundant and therefore, loss of CD28 due to both replicative senescence and cytokine exposure may not be mutually exclusive in inflammatory disorders (10). Moreover, increased TNF-α is one of the features of inflammaging, which is a low-grade, chronic, systemic pro-inflammatory state frequently observed in the elderly that is associated with the unexpected upregulation of proinflammatory responses later in life (10242526). Although CD4 + T cells are more resistant to age-associated phenotypic and functional changes than CD8 T cells, CD4 + CD28 − T cells is also increased with advancing age in healthy individuals (9).…”

“…The molecular mechanisms controlling CD28 expression and loss appear to be similar in both T-cell subsets, but the age-associated accumulation of CD28 − T cells is more prominent in CD8 T cells than CD4 T cells (89). Expansion of CD4 + CD28 − T cells in part reflects the infectious burden from latent viral infections such as CMV and EBV and leads to generating memory inflation in the elderly (10). Accumulating evidence reveals that there is a significant age-inappropriate expansion of cytotoxic CD4 + CD28 − T cells in patients with a variety of chronic inflammatory diseases, suggesting that these cells might play a role in the pathogenesis of these immune disorders (1112131415).…”

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

“…The decline of the immune system with age is reflected by increased frequencies of infection, cancer, cardiovascular disease, and neurodegenerative disease (Sarkar and Fisher 2006;Targonski et al 2007;Yu et al 2015). Both innate and adaptive immune responses are affected by the aging process; however, the adaptive response seems to be especially affected by age-related changes in the immune system.…”

Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) cohort: study protocol and results of the first 3 years of enrollment

“…These immunological characteristics and clinical features are analyzed using fluorescence-activated cell sorting analysis and enzyme-linked immunosorbent assays [26] for subsamples of the participants enrolled at each clinic. Chronic inflammation has been established to be responsible for the development of CVD [27], meaning that it may be a therapeutic target.…”