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

Chen, Hung-Chang; Eling, Nils; Martínez-Jiménez, Celia P.; O'Brien, L. M.; Carbonaro, Valentina; Marioni, John C.; Odom, Duncan T.

doi:10.15252/embr.201847379

Cited by 41 publications

(35 citation statements)

References 77 publications

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“…4 b,d). γδ T cells were more rare and, in contrast to islets, decreased modestly from 2.4 to 1.4% with age, which has been previously reported [ 39 ]. Also unlike in islets, regulatory T cells increased modestly with age, while the NKT cell fraction was unaltered.…”

Section: Resultssupporting

confidence: 76%

T cells accumulate in non-diabetic islets during ageing

et al. 2021

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Background The resident immune population of pancreatic islets has roles in islet development, beta cell physiology, and the pathology of diabetes. These roles have largely been attributed to islet macrophages, comprising 90% of islet immune cells (in the absence of islet autoimmunity), and, in the case of type 1 diabetes, to infiltrating autoreactive T cells. In adipose, tissue-resident and recruited T and B cells have been implicated in the development of insulin resistance during diet-induced obesity and ageing, but whether this is paralleled in the pancreatic islets is not known. Here, we investigated the non-macrophage component of resident islet immune cells in islets isolated from C57BL/6 J male mice during ageing (3 to 24 months of age) and following similar weight gain achieved by 12 weeks of 60% high fat diet. Immune cells were also examined by flow cytometry in cadaveric non-diabetic human islets. Results Immune cells comprised 2.7 ± 1.3% of total islet cells in non-diabetic mouse islets, and 2.3 ± 1.7% of total islet cells in non-diabetic human islets. In 3-month old mice on standard diet, B and T cells each comprised approximately 2–4% of the total islet immune cell compartment, and approximately 0.1% of total islet cells. A similar amount of T cells were present in non-diabetic human islets. The majority of islet T cells expressed the αβ T cell receptor, and were comprised of CD8-positive, CD4-positive, and regulatory T cells, with a minor population of γδ T cells. Interestingly, the number of islet T cells increased linearly (R2 = 0.9902) with age from 0.10 ± 0.05% (3 months) to 0.38 ± 0.11% (24 months) of islet cells. This increase was uncoupled from body weight, and was not phenocopied by a degree similar weight gain induced by high fat diet in mice. Conclusions This study reveals that T cells are a part of the normal islet immune population in mouse and human islets, and accumulate in islets during ageing in a body weight-independent manner. Though comprising only a small subset of the immune cells within islets, islet T cells may play a role in the physiology of islet ageing.

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Section: Resultssupporting

confidence: 76%

T cells accumulate in non-diabetic islets during ageing

et al. 2021

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“…77 This might be related to a selective expansion of Vγ6 + cells that was reported in the peripheral lymph nodes and spleen of older mice, which takes place in parallel with increasing IL-17 polarization of Vγ4 + γδ T cells. 78 Alternatively, a recent study examining γδ T cells that reside in the gingiva presented evidence that the Vγ6/Vγ4 balance in this tissue depends at least partially on the presence of commensal bacteria. It showed that in germ-free mice, gingival Vγ6 + cells, which normally predominate, were diminished, whereas the number of gingival Vγ4 + numbers was increased.…”

Section: Dis Tributionmentioning

confidence: 99%

Two functionally distinct subsets of IL‐17 producing γδ T cells

O’Brien

Born

2020

Immunological Reviews

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The γδ T cells play an important role in both mice and humans as a source of the cytokine IL-17, which is key for immune resistance to certain pathogens. In mice, most of these IL-17 producers, termed γδT-17 cells, actually comprise two distinct types: those expressing an invariant Vγ6Vδ1 + TCR and those expressing a Vγ4 + TCR. Murine γδT-17 cells acquire an inherent bias to produce IL-17 and other "type 17" cytokines during thymic development. The similarities and differences between the two mouse γδT-17 types are reviewed here, and the potential implications of their differences are discussed. There is some evidence that two distinct TCR-defined IL-17-producing γδ T cell subsets also exist in humans, but unlike the mouse γδT-17 cells, these cells are probably not imprinted with an IL-17 bias during thymic development, but rather acquire an IL-17 bias in the periphery. K E Y W O R D S host defense, IL-17, IL-22, thymic development, type 17 cytokines, type 3 immunity, γδ T cell memory, γδ T cells, γδT-17 cells How to cite this article: O'Brien RL, Born WK. Two functionally distinct subsets of IL-17 producing γδ T cells.

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“…The nature of these signals, which lead to a down‐regulation of CD69 and increased S1PR1 expression, remains elusive . Therefore, and although this current study did not observe any impact of housing conditions in diverse animal facilities, it appears likely that skin microbiota and exposure to pathogens are critically involved. Germ‐free mice showed a specific decrease of Vγ6 + T‐cell numbers in mucosal tissues but also in skin‐draining lymph nodes .…”

Section: Altered Composition Of the γδ T‐cell Pool In Lymph Nodes Durmentioning

confidence: 54%

Dangerous γδ T cells in aged mice

Prinz

Sandrock

2019

EMBO Reports

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Progressive susceptibility to tumors and infectious diseases in the elderly are a serious threat to public health in aging societies. For this reason, there is growing interest in mechanisms and predictive biomarkers that accompany and potentially cause this process. In this issue of EMBO Reports, Chen et al [1] report the surprising finding that a specific subset of γδ T cells with very limited clonal diversity strongly expands in lymph nodes of aging mice. These T cells uniformly express a T‐cell receptor (TCR) composed of a Vγ6 and a Vδ1 chain and show an effector T‐cell phenotype characterized by the swift production of the pro‐inflammatory cytokine interleukin‐17 (IL‐17) upon ex vivo stimulation (γδT17 cells). Since γδT17 cells are suspected to be pro‐tumorigenic [2], the authors next compared how mice of different age coped with an experimental lung cancer challenge and found impaired anti‐tumor responses in old mice. Based on these observations, they propose a link between changes of the composition of γδ T cells in the aging lymph nodes and increased risk of cancer development in aged mice.

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

Cited by 41 publications

References 77 publications

T cells accumulate in non-diabetic islets during ageing

T cells accumulate in non-diabetic islets during ageing

Two functionally distinct subsets of IL‐17 producing γδ T cells

Dangerous γδ T cells in aged mice

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