Senescent T cells: Beneficial and detrimental roles

Laphanuwat, Phatthamon; Gomes, Daniel Cláudio Oliveira; Akbar, Arne N.

doi:10.1111/imr.13206

Cited by 12 publications

(6 citation statements)

References 188 publications

(447 reference statements)

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“…Immunity also declines during aging. This is highlighted by the increased incidence of malignancy, loss of immunity to previously encountered pathogens [13]. It is recognized widely that the activation by persistent viruses such as cytomegalovirus (CMV) in vivo could make the proportion of naive T cells decrease during aging and the proportion of senescent cells like TEMRA cells increase [14][15][16].…”

Section: Resultsmentioning

confidence: 99%

The level of IL-8 in TMERA cells as a biomarker for hormonotherapy in thymoma

Yu,

Cui

et al. 2023

Preprint

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Thymoma is the most common type of neoplasm in the anterior mediastinum. However, it can be challenging to differentiate thymoma from other anterior mediastinum tumors in this region through imaging examinations. Therefore, the identification of a reliable, unique characteristic for the further study of thymoma is crucial. Our study confirms an increase in TEMRA cells in type B thymoma and suggests that the level of IL-8 in TEMRA cells may be a biomarker indicating hormonotherapy can be an effective treatment for patients with type B1 and B2 thymoma patients.

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Section: Resultsmentioning

confidence: 99%

The level of IL-8 in TMERA cells as a biomarker for hormonotherapy in thymoma

Yu,

Cui

et al. 2023

Preprint

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“…These impaired tissue responses may result in reduced immune surveillance of an organ and predispose for tumor formation with age as observed for lung and colon cancer– diseases of the elderly 69 . The increased systemic inflammation and cytotoxicity of surveilling T and NK populations can have both deleterious effects causing tissue damage, but can also help clear senescent cells 70,71 . Our results also reveal a potential switch to more T cell proliferation and tissue repair functions with age in LN, possibly in response to age-associated tissue damage.…”

Section: Discussionmentioning

confidence: 99%

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

Wells,

Rainbow,

Mark

et al. 2024

Preprint

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The immune system comprises multiple cell lineages and heterogeneous subsets found in blood and tissues throughout the body. While human immune responses differ between sites and over age, the underlying sources of variation remain unclear as most studies are limited to peripheral blood. Here, we took a systems approach to comprehensively profile RNA and surface protein expression of over 1.25 million immune cells isolated from blood, lymphoid organs, and mucosal tissues of 24 organ donors aged 20-75 years. We applied a multimodal classifier to annotate the major immune cell lineages (T cells, B cells, innate lymphoid cells, and myeloid cells) and their corresponding subsets across the body, leveraging probabilistic modeling to define bases for immune variations across donors, tissue, and age. We identified dominant tissue-specific effects on immune cell composition and function across lineages for lymphoid sites, intestines, and blood-rich tissues. Age-associated effects were intrinsic to both lineage and site as manifested by macrophages in mucosal sites, B cells in lymphoid organs, and T and NK cells in blood-rich sites. Our results reveal tissue-specific signatures of immune homeostasis throughout the body and across different ages. This information provides a basis for defining the transcriptional underpinnings of immune variation and potential associations with disease-associated immune pathologies across the human lifespan.

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“…IL-15 was shown to activate promyelocytic leukemia zinc finger (PLZF) transcription factor, which upregulates NKRs on memory CD8 + T cells ( 72 ). Senescent CD8 + T cells are characterized by enhanced NK cell-like functions mediated by NK-activating receptors ( 73 ). Sestrins are stress-sensing proteins produced in response to glucose deprivation, oxidative stress, or cellular senescence ( 74 ).…”

Section: Il-15 and T-cell Responsesmentioning

confidence: 99%

“…Thus, the poor sensitivity to TCR signals and enhanced responsiveness to IL-15 render senescent CD8 + T cells sensitive to TCR-independent, IL-15-induced activation. This may explain the loss of immunity to previously encountered pathogens, decreased vaccine efficacy, and enhanced immunopathological tissue injury often demonstrated in aged individuals ( 73 ). Further work is required to elucidate the molecular mechanisms underlying IL-15 hyper-responsiveness and the resulting NK-like functions of senescent CD8 + T cells.…”

Section: Il-15 and T-cell Responsesmentioning

confidence: 99%

IL-15 in T-Cell Responses and Immunopathogenesis

Lee,

Park,

Shin

2024

Immune Netw

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IL-15 belongs to the common gamma chain cytokine family and has pleiotropic immunological functions. IL-15 is a homeostatic cytokine essential for the development and maintenance of NK cells and memory CD8 + T cells. In addition, IL-15 plays a critical role in the activation, effector functions, tissue residency, and senescence of CD8 + T cells. IL-15 also activates virtual memory T cells, mucosal-associated invariant T cells and γδ T cells. Recently, IL-15 has been highlighted as a major trigger of TCR-independent activation of T cells. This mechanism is involved in T cell-mediated immunopathogenesis in diverse diseases, including viral infections and chronic inflammatory diseases. Deeper understanding of IL-15-mediated T-cell responses and their underlying mechanisms could optimize therapeutic strategies to ameliorate host injury by T cell-mediated immunopathogenesis. This review highlights recent advancements in comprehending the role of IL-15 in relation to T cell responses and immunopathogenesis under various host conditions.

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Senescent T cells: Beneficial and detrimental roles

Cited by 12 publications

References 188 publications

The level of IL-8 in TMERA cells as a biomarker for hormonotherapy in thymoma

The level of IL-8 in TMERA cells as a biomarker for hormonotherapy in thymoma

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

IL-15 in T-Cell Responses and Immunopathogenesis

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