The Impact of T-cell Aging on Alloimmunity and Inflammaging

Iske, Jasper; Dedeilia, Aikaterini; Xiao, Yao; Martin, Friederike; Emmert, MY; Sage, Peter T.; Abdi, Reza; Zhou, Hao; Tullius, Stefan G.

doi:10.1097/tp.0000000000004715

Cited by 2 publications

(1 citation statement)

References 113 publications

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“…This type of immunesenescence results in a state of anergy that is readily broken with strong cytokine stimulation, such as would be seen with infections (121). Thus, while lower rates of acute graft rejection may be seen in STS transplant recipients, these recipients are at continued risk of chronic rejection (122,123).…”

Section: Graft-specific Complicationsmentioning

confidence: 99%

Immune aging: biological mechanisms, clinical symptoms, and management in lung transplant recipients

Kapse,

Budev,

Singer

et al. 2024

Front. Transplant.

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While chronologic age can be precisely defined, clinical manifestations of advanced age occur in different ways and at different rates across individuals. The observed phenotype of advanced age likely reflects a superposition of several biological aging mechanisms which have gained increasing attention as the world contends with an aging population. Even within the immune system, there are multiple age-associated biological mechanisms at play, including telomere dysfunction, epigenetic dysregulation, immune senescence programs, and mitochondrial dysfunction. These biological mechanisms have associated clinical syndromes, such as telomere dysfunction leading to short telomere syndrome (STS), and optimal patient management may require recognition of biologically based aging syndromes. Within the clinical context of lung transplantation, select immune aging mechanisms are particularly pronounced. Indeed, STS is increasingly recognized as an indication for lung transplantation. At the same time, common aging phenotypes may be evoked by the stress of transplantation because lung allografts face a potent immune response, necessitating higher levels of immune suppression and associated toxicities, relative to other solid organs. Age-associated conditions exacerbated by lung transplant include bone marrow suppression, herpes viral infections, liver cirrhosis, hypogammaglobulinemia, frailty, and cancer risk. This review aims to dissect the molecular mechanisms of immune aging and describe their clinical manifestations in the context of lung transplantation. While these mechanisms are more likely to manifest in the context of lung transplantation, this mechanism-based approach to clinical syndromes of immune aging has broad relevance to geriatric medicine.

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Section: Graft-specific Complicationsmentioning

confidence: 99%

Immune aging: biological mechanisms, clinical symptoms, and management in lung transplant recipients

Kapse,

Budev,

Singer

et al. 2024

Front. Transplant.

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Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs

Kirchner,

Badshah,

Hong

et al. 2023

Transplantation

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Aging of the world population significantly impacts healthcare globally and specifically, the field of transplantation. Together with end-organ dysfunction and prolonged immunosuppression, age increases the frequency of comorbid chronic diseases in transplant candidates and recipients, contributing to inferior outcomes. Although the frequency of death increases with age, limited use of organs from older deceased donors reflects the concerns about organ durability and inadequate function. Cellular senescence (CS) is a hallmark of aging, which occurs in response to a myriad of cellular stressors, leading to activation of signaling cascades that stably arrest cell cycle progression to prevent tumorigenesis. In aging and chronic conditions, senescent cells accumulate as the immune system’s ability to clear them wanes, which is causally implicated in the progression of chronic diseases, immune dysfunction, organ damage, decreased regenerative capacity, and aging itself. The intimate interplay between senescent cells, their proinflammatory secretome, and immune cells results in a positive feedback loop, propagating chronic sterile inflammation and the spread of CS. Hence, senescent cells in organs from older donors trigger the recipient’s alloimmune response, resulting in the increased risk of graft loss. Eliminating senescent cells or attenuating their inflammatory phenotype is a novel, potential therapeutic target to improve transplant outcomes and expand utilization of organs from older donors. This review focuses on the current knowledge about the impact of CS on circulating immune cells in the context of organ damage and disease progression, discusses the impact of CS on abdominal solid organs that are commonly transplanted, and reviews emerging therapies that target CS.

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The Impact of T-cell Aging on Alloimmunity and Inflammaging

Cited by 2 publications

References 113 publications

Immune aging: biological mechanisms, clinical symptoms, and management in lung transplant recipients

Immune aging: biological mechanisms, clinical symptoms, and management in lung transplant recipients

Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs

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