Human liver infiltrating γδ T cells are composed of clonally expanded circulating and tissue-resident populations

Journal of Hepatology
Stuart HunterBenjamin E Willcox

Abstract

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. 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. 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 di...Continue Reading

Citations

Jan 22, 2019·Nature Immunology·Benjamin E Willcox, Carrie R Willcox
Apr 19, 2019·PLoS Pathogens·Kyong-Mi ChangUNKNOWN Hepatitis B Research Network (HBRN)
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Datasets Mentioned

BETA
SRP113556

Methods Mentioned

BETA
flow cytometry
density gradient centrifugation
Assay
PCR
PMA
of

Software Mentioned

VDJTools
MiXCR
IMGT Junction Analysis
Summit
Graphpad
FlowJo
TreeStar
Graphpad PRISM
iRweb
R

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