Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells

Kallemeijn, Martine J.; Boots, A.; Klift, Michèle Y. van der; Brouwer, Elisabeth; Abdulahad, Wayel H.; Verhaar, Jan A N; Dongen, Jacques J. M. van; Langerak, Anton W.

doi:10.1038/s41598-017-05849-1

Cited by 41 publications

(46 citation statements)

References 72 publications

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“…Interestingly, a shift towards more effector phenotypes, largely maintained TCR diversity and a change in Vγ/Vδ usage has also been detected in the peripheral blood of humans upon organismal ageing , suggesting similar age‐related processes occurring in the murine and human γδ T‐cell pool.…”

Section: Discussionmentioning

confidence: 86%

IL ‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response

et al. 2019

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How the age‐associated decline of immune function leads to increased cancer incidence is poorly understood. Here, we have characterised the cellular composition of the γδ T‐cell pool in peripheral lymph nodes ( pLN s) upon ageing. We find that ageing has minimal cell‐intrinsic effects on function and global gene expression of γδ T cells, and γδ TCR diversity remains stable. However, ageing alters TCR δ chain usage and clonal structure of γδ T‐cell subsets. Importantly, IL ‐17‐producing γδ17 T cells dominate the γδ T‐cell pool of aged mice—mainly due to the selective expansion of Vγ6 + γδ17 T cells and augmented γδ17 polarisation of Vγ4 + T cells. Expansion of the γδ17 T‐cell compartment is mediated by increased IL ‐7 expression in the T‐cell zone of old mice. In a Lewis lung cancer model, pro‐tumourigenic Vγ6 + γδ17 T cells are exclusively activated in the tumour‐draining LN and their infiltration into the tumour correlates with increased tumour size in aged mice. Thus, upon ageing, substantial compositional changes in γδ T‐cell pool in the pLN lead to an unbalanced γδ T‐cell response in the tumour that is associated with accelerated tumour growth.

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Section: Discussionmentioning

confidence: 86%

IL ‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response

et al. 2019

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“…faster, suggesting a memory-like phenotype. 113 In sum, results from in vitro and natural infection studies suggest an important role for cd T cells in controlling influenza, HIV and CMV viral replication. 111,112 These results suggest that cd T cells are important mediators of protection against CMV and support approaches using adoptive transfer of effector/memory cd T cells or targeting cd T cells in future CMV vaccine trials.…”

Section: Viral Infectionsmentioning

confidence: 97%

“…The possibility of inducing exhausted cd T cells would need to be considered, however, as CMV infection has both been shown to result in higher numbers of these cells. 113 In sum, results from in vitro and natural infection studies suggest an important role for cd T cells in controlling influenza, HIV and CMV viral replication. Targeting cd T cells through stimulation could provide an important adjuvanttype role in vaccination and/or cure-related strategies for viral infections.…”

Section: Viral Infectionsmentioning

confidence: 97%

Emerging role of γδ T cells in vaccine‐mediated protection from infectious diseases

2019

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γδ T cells are fascinating cells that bridge the innate and adaptive immune systems. They have long been known to proliferate rapidly following infection; however, the identity of the specific γδ T cell subsets proliferating and the role of this expansion in protection from disease have only been explored more recently. Several recent studies have investigated γδ T‐cell responses to vaccines targeting infections such as Mycobacterium, Plasmodium and influenza, and studies in animal models have provided further insight into the association of these responses with improved clinical outcomes. In this review, we examine the evidence for a role for γδ T cells in vaccine‐induced protection against various bacterial, protozoan and viral infections. We further discuss results suggesting potential mechanisms for protection, including cytokine‐mediated direct and indirect killing of infected cells, and highlight remaining open questions in the field. Finally, building on current efforts to integrate strategies targeting γδ T cells into immunotherapies for cancer, we discuss potential approaches to improve vaccines for infectious diseases by inducing γδ T‐cell activation and cytotoxicity.

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“…Using these surface markers, αβ T cells are known to have a higher frequency of highly differentiated and replicative senescent T cells in circulation with aging, denoted by the surface marker CD57 that implies impairment in their ability to proliferate [118]. However, our recent studies, along with others, have shown that while pan-γδ T cells do not express the same phenotypic changes as αβ T cells during aging [119,120]; the frequencies of γδ T cell subsets, particularly the Vδ2+ subset, decrease with age after age 30. However, the extent of the latter is influenced by sex and nationality [121][122][123][124] (Figure 3b).…”

Section: Homeostasis Of γδ T Cells In Tissuesmentioning

confidence: 91%

The Aging of γδ T Cells

Lau

Fülöp

et al. 2020

Cells

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In the coming decades, many developed countries in the world are expecting the "greying" of their populations. This phenomenon poses unprecedented challenges to healthcare systems. Aging is one of the most important risk factors for infections and a myriad of diseases such as cancer, cardiovascular and neurodegenerative diseases. A common denominator that is implicated in these diseases is the immune system. The immune system consists of the innate and adaptive arms that complement each other to provide the host with a holistic defense system. While the diverse interactions between multiple arms of the immune system are necessary for its function, this complexity is amplified in the aging immune system as each immune cell type is affected differently-resulting in a conundrum that is especially difficult to target. Furthermore, certain cell types, such as γδ T cells, do not fit categorically into the arms of innate or adaptive immunity. In this review, we will first introduce the human γδ T cell family and its ligands before discussing parallels in mice. By covering the ontogeny and homeostasis of γδ T cells during their lifespan, we will better capture their evolution and responses to age-related stressors. Finally, we will identify knowledge gaps within these topics that can advance our understanding of the relationship between γδ T cells and aging, as well as age-related diseases such as cancer.Their well-characterized roles further imply the physiological importance of age-associated T-cell adaptations, which garners the widespread scientific interest that has contributed to the current depth of T-cell-related investigations [14,15].T cells can essentially be classified into the adaptive arm, although minority subsets exhibit an innate phenotype. Adaptive T cells include those expressing an αβ T cell receptor (TCR) at their surface and "innate-like" T cells are comprised of T cells expressing a γδ TCR, mucosal associated invariant T (MAIT), invariant natural killer T (iNKT) and germline-encoded mycolyl lipid-reactive (GEMT) [16]. This classification is based on their response speed when encountering new antigens and the ability to form memory cells that persist in long-term immunosurveillance. In this review, we will focus on γδ T cells and their contextual importance in cancer immunosurveillance, and on the reactivation of latent infections such as tuberculosis and virus-infected cells, as these topics require consolidation in the literature but are often neglected in the aging context.First, we will describe γδ T cells and their respective ligands in both mice and human. Next, we will analyze γδ T cells from cradle to grave (i.e., development to old age) to understand their aging trajectory during lifespan. Finally, we will suggest future developments that are necessary for our comprehension of how γδ T cells subsets are affected during the aging process. A better understanding of γδ T cell biology should enable scientists to tailor optimized immunotherapy that targets age-associated immune impairments in th...

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Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells

Cited by 41 publications

References 72 publications

IL ‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response

IL ‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response

Emerging role of γδ T cells in vaccine‐mediated protection from infectious diseases

The Aging of γδ T Cells

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