Human liver infiltrating cd T c expanded circulating and t

Background & Aims:cd T cells comprise a substantial proportion of tissue-associated lymphocytes. However, our current understanding of human cd T cells is primarily based on peripheral blood subsets, while the immunobiology of tissueassociated subsets remains largely unclear. Therefore, we aimed to elucidate the T cell receptor (TCR) diversity, immunophenotype and function of cd T cells in the human liver. Methods:We characterised the TCR repertoire, immunophenotype and function of human liver infiltrating cd T cells, by TCR sequencing analysis, flow cytometry, in situ hybridisation and immunohistochemistry. We focussed on the predominant tissue-associated Vd2 cd subset, which is implicated in liver immunopathology. Results: Intrahepatic Vd2 cd 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 effector lymphocytes, whereas naïve CD27, TCR-diverse populations present in matched blood were generally absent in the liver. Furthermore, while a CD45RA Vd2 cd effector subset present in both liver and peripheral blood contained overlapping TCR clonotypes, the liver Vd2 cd T cell pool also included a phenotypically distinct CD45RA 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 Vd2 cd cells were capable of polyfunctional cytokine secretion, and unlike peripheral blood subsets, were responsive to both TCR and innate stimuli.