Markers of T Cell Senescence in Humans

Abstract

Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to infections, cardiovascular and neurodegenerative disease, cancer as well as reduced efficacy of vaccination are important matters for researchers in the field of aging. As older adults show higher prevalence for a variety of diseases, this also implies higher risk of complications, including nosocomial infections, slower recovery and sequels that may reduce the autonomy and overall quality of life of older adults. The age-related effects on the immune system termed as "immunosenescence" can be exemplified by the reported hypo-responsiveness to influenza vaccination of the elderly. T cells, which belong to the adaptive arm of the immune system, have been extensively studied and the knowledge gathered enables a better understanding of how the immune system may be affected after acute/chronic infections and how this matters in the long run. In this review, we will focus on T cells and discuss the surface and molecular markers that are associated with T cell senescence. We will also look at the implications that senescent T cells could have on human health and diseases. Finally, we will discuss the benefits of having these markers for investigators and the future work that is needed to advance the field of T cell senescence markers.

Type 2 diabetes is associated with the accumulation of senescent T cells

“…Here we conclusively dem onstrate that while people living with T2D exhibit lym phopaenia the remaining T cells present are the senescent EMRA subset of CD4 + and CD8 + T cells. Senescent T cell have been well documented to be a proinflammatory subset [14] secreting their own unique array of proinflammatory products as part of their SASP [33], reinforcing both the senescent and inflammatory phenotype of these cells. The inflammatory environment of T2D, evidenced here as a measurable rise in serum markers of inflammation, further contributes to the gen eration of senescent T cells.…”

“…This theory has also gained traction in studies observing the effects of met formin, where both murine [10] and human studies [11] have shown a survival advantage with metformin treatment, theorized to be a consequence of inhibiting the SASP production by modulating the activation of the nuclear factor kappa B (NFκB) proinflammatory pathway [12]. Senescent T cells can be defined on the basis of surface marker expression, such as the loss of the costimulatory molecules CD27 and CD28 or the homing marker CCR7 and the reexpression of CD45RA, together with elevated levels of viralspecific makers CD57 and killer cell lectin like receptor G1 (KLRG1) [13,14]. While senescent T cells show proliferative impairment their ability to secrete pro inflammatory cytokines such as interferon (IFN)γ and tumour necrosis factor (TNF)α are retained [14][15][16].…”

“…Senescent T cells can be defined on the basis of surface marker expression, such as the loss of the costimulatory molecules CD27 and CD28 or the homing marker CCR7 and the reexpression of CD45RA, together with elevated levels of viralspecific makers CD57 and killer cell lectin like receptor G1 (KLRG1) [13,14]. While senescent T cells show proliferative impairment their ability to secrete pro inflammatory cytokines such as interferon (IFN)γ and tumour necrosis factor (TNF)α are retained [14][15][16].…”

Vaccine-induced ICOS+CD38+ cTfh are sensitive biosensors of age-related changes in inflammatory pathways

“…Influenza vaccination induces strain-specific neutralizing antibodies in healthy adults, but this process is impaired with aging (1)(2)(3)(4). Moreover, immunological aging, that may or may not be directly linked to chronological aging, is also associated with increased morbidity and mortality from infectious diseases (5,6). Studies of immunological aging and vaccines have identified mechanisms including alterations at the subcellular (7,8), cellular (9,10), and systems levels (11)(12)(13)(14) that lead to altered vaccine responses.…”

Age related defects in NK cell immunity revealed by deep immune profiling of pediatric cancer patients

“…The magnitude of these changes in differentiation status, relative to age matched healthy children, were striking with frequencies of TEMRA in older children resembling those in healthy middle aged adults. Although we did not measure the functional capacity of TEMRA cells in cancer patients, they were largely negative for CD57 ( Si Fig 8), a marker of terminally differentiated T-cells that have short telomeres, high apoptosis sensitivity and replicative senescence 56 . These expanded memory and TEMRA T-cells are therefore likely to be functional.…”