Abstract:
BACKGROUND & AIMS:γδ T cells comprise a substantial proportion of tissue-associated lymphocytes. However, our current understanding of human γδ T cells is primarily based on peripheral blood subsets, while the immunobiology of tissue-associated subsets remains largely unclear. Therefore, we aimed to elucidate the T cell receptor (TCR) diversity, immunophenotype and function of γδ T cells in the human liver. METHODS:We characterised the TCR repertoire, immunophenotype and function of human liver infiltrating γδ T cells, by TCR sequencing analysis, flow cytometry, in situ hybridisation and immunohistochemistry. We focussed on the predominant tissue-associated Vδ2- γδ subset, which is implicated in liver immunopathology. RESULTS:Intrahepatic Vδ2- γδ T cells were highly clonally focussed, with single expanded clonotypes featuring complex, private TCR rearrangements frequently dominating the compartment. Such T cells were predominantly CD27lo/- effector lymphocytes, whereas naïve CD27hi, TCR-diverse populations present in matched blood were generally absent in the liver. Furthermore, while a CD45RAhi Vδ2- γδ effector subset present in both liver and peripheral blood contained overlapping TCR clonotypes, the liver Vδ2- γδ T cell pool also included a phenotypically distinct CD45RAlo effector compartment that was enriched for expression of the tissue tropism marker CD69, the hepatic homing chemokine receptors CXCR3 and CXCR6, and liver-restricted TCR clonotypes, suggestive of intrahepatic tissue residency. Liver infiltrating Vδ2- γδ cells were capable of polyfunctional cytokine secretion, and unlike peripheral blood subsets, were responsive to both TCR and innate stimuli. CONCLUSION:These findings suggest that the ability of Vδ2- γδ T cells to undergo clonotypic expansion and differentiation is crucial in permitting access to solid tissues, such as the liver, which results in functionally distinct peripheral and liver-resident memory γδ T cell subsets. They also highlight the inherent functional plasticity within the Vδ2- γδ T cell compartment and provide information that could be used for the design of cellular therapies that suppress liver inflammation or combat liver cancer. LAY SUMMARY:γδ T cells are frequently enriched in many solid tissues, however the immunobiology of such tissue-associated subsets in humans has remained unclear. We show that intrahepatic γδ T cells are enriched for clonally expanded effector T cells, whereas naïve γδ T cells are largely excluded. Moreover, whereas a distinct proportion of circulating T cell clonotypes was present in both the liver tissue and peripheral blood, a functionally and clonotypically distinct population of liver-resident γδ T cells was also evident. Our findings suggest that factors triggering γδ T cell clonal selection and differentiation, such as infection, can drive enrichment of γδ T cells into liver tissue, allowing the development of functionally distinct tissue-restricted memory populations specialised in local hepatic immunosurveillance.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Hunter S,Willcox CR,Davey MS,Kasatskaya SA,Jeffery HC,Chudakov DM,Oo YH,Willcox BEdoi
10.1016/j.jhep.2018.05.007subject
Has Abstractpub_date
2018-09-01 00:00:00pages
654-665issue
3eissn
0168-8278issn
1600-0641pii
S0168-8278(18)32053-1journal_volume
69pub_type
杂志文章abstract::Alcohol use disorders (AUDs) is one of the leading causes of disease and disability in almost all European countries. Among the alcohol-related diseases, alcoholic liver disease (ALD) is the most common. At present, alcohol is the most frequent cause of liver cirrhosis in the Western world. The cornerstone of treatmen...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2016.04.029
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND/AIMS:Primary and secondary liver tumours are a common clinical problem, with a poor prognosis in most cases. Surgical resection offers the best outcome, but is only appropriate for the minority. Thermal ablation techniques have been described, but the lack of an optimal means of monitoring has limited their ...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(99)80234-7
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND & AIMS:Autophagy plays a crucial role in hepatic homeostasis and its deregulation has been associated with chronic liver disease. However, the effect of autophagy on the release of fibrogenic extracellular vesicles (EVs) by platelet-derived growth factor (PDGF)-stimulated hepatic stellate cells (HSCs) remain...
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doi:10.1016/j.jhep.2020.04.044
更新日期:2020-11-01 00:00:00
abstract::It has been suggested that the cellular immune response to HBV antigens is responsible for hepatocellular injury in acute and chronic hepatitis B. However, definitive immunological studies have so far been hampered by the lack of appropriate model systems to study HBV antigen-specific T cells. The availability of high...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(88)80503-8
更新日期:1988-08-01 00:00:00
abstract:BACKGROUND/AIM:Anti-neutrophil cytoplasmic antibodies (ANCA) are a group of autoantibodies first associated with Wegener's granulomatosis and microscopic polyangiitis. The significance of ANCA in autoimmune hepatitis remains uncertain; the nature of the antigen or antigens has not been defined yet. The purpose of this ...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(97)80007-4
更新日期:1997-01-01 00:00:00
abstract::Drug hepatotoxicity is partially determined by genetic factors involved in drug metabolism, which may involve the debrisoquine oxidation polymorphism mediated by cytochrome (CYP) 2D6. The purpose of this study was to assess the relationship between drug hepatotoxicity and another genetic polymorphism of drug oxidation...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80620-8
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND/AIMS:Liver fibrosis is a dynamic state between matrix production and degradation. Since our report in 1974, many studies have examined collagenase and liver fibrosis, but not the identification of cells responsible for collagenase production in vivo. The aim of this study was to investigate the gene expressi...
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pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80363-3
更新日期:2000-08-01 00:00:00
abstract::Liver transplantation is performed successfully across major HLA differences between donor and recipient. This may be influenced by the organ specific expression of major histocompatibility complex (MHC) molecules which determine the local immune reactivity and rejection response. The tissue expression of MHC molecule...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/0168-8278(90)90264-r
更新日期:1990-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.jhep.2019.06.032
更新日期:2019-12-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.02.007
更新日期:2020-07-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.03.024
更新日期:2011-12-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.03.034
更新日期:2014-08-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jhep.2008.12.023
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND/AIMS:Chronic graft hepatitis occurs in 20-30% adults after liver transplantation but the prevalence and causes in children are not known. In adults, hepatitis C virus infection is prevalent prior to transplantation and recurrent infection is a frequent cause of graft dysfunction. The significance of the rece...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80225-0
更新日期:1998-05-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.07.017
更新日期:2016-12-01 00:00:00
abstract::The First European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients aimed to produce recommendations that could be applied across Europe. However, some important differences exist around Europe, in terms of access to treatment and tests for monitoring. This short survey of...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2005.11.034
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND/AIMS:No study has compared the liver fibrosis progression rates among chronic liver diseases and the risk factors in order to better organize screening strategies. METHODS:A total of 4852 patients were retrospectively studied (chronic hepatitis C (HCV) [n=2313], human immunodeficiency virus (HIV)-HCV co-inf...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00413-0
更新日期:2003-03-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.12.005
更新日期:2016-05-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.05.026
更新日期:2013-10-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2008.01.006
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pub_type: 杂志文章
doi:10.1016/s0168-8278(94)80235-1
更新日期:1994-11-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80210-8
更新日期:1996-10-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2021.01.014
更新日期:2021-01-20 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80284-0
更新日期:1999-11-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.02.016
更新日期:2005-07-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.06.019
更新日期:2013-11-01 00:00:00
abstract::The effect of glucagon on the relation between urea synthesis and blood amino acid concentration was studied in seven healthy volunteers. Alanine was given as prime-continuous infusions and, after 1 hr for equilibration, the urea nitrogen synthesis rate was measured in two periods of about 2 hrs as urinary excretion c...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90072-y
更新日期:1990-01-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80138-9
更新日期:1997-12-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.08.023
更新日期:2017-09-21 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.04.010
更新日期:2017-09-01 00:00:00