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

作者：Stuart Hunter, Carrie R. Willcox, Martin S. Davey, Sofya A. Kasatskaya, Hannah C. Jeffery, Dmitriy M. Chudakov, Ye Htun Oo, Benjamin E. Willcox · 发表于：Journal of Hepatology · 年份：2018 · DOI：10.1016/j.jhep.2018.05.007 · 被引用次数：163 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Diabetes and associated disorders

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 CD27 lo/− effector lymphocytes, whereas naïve CD27 hi , TCR-diverse populations present in matched blood were generally absent in the liver. Furthermore, while a CD45RA hi 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 CD45RA lo 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 o...