Abstract
Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103. CD69 + CD8+ T cells expressed low levels of S1PR1 and KLF2 and a large proportion (>90%) was CXCR6+, resembling liver TRM in mice and liver resident NK cells in human. Cytotoxic proteins were only expressed in a small fraction of liver CD69 + CD8+ T cells in patients without viral hepatitis, however, in livers from CHB patients more CD69 + CD8+ T cells were granzyme B+. In CHC patients, less intrahepatic CD69 + CD8+ T cells were Hobit+ as compared to CHB and control patients. Intrahepatic CD69 + CD8+ T cells likely TRM which have a reduced cytolytic potential. In patients with chronic viral hepatitis TRM have a distinct phenotype.
Highlights
Whereas previous data has identified a large CD69 + NK cell population in the liver[10], data on CD8+ T cells with a tissue resident phenotype in the human liver is lacking, as is knowledge on their phenotype in patients with viral hepatitis
In this study we have for the first time in man characterized a population of CD69 + CD8+ T cells with a tissue resident-like phenotype which is abundantly present in the liver, but not in the peripheral blood
Subsets of human TRM including those in lung, brain, skin and gut[3, 24] co-express CD103, which forms a heterodimer with integrin β7 and recognizes E-cadherin, which is expressed on hepatocytes and bile duct epithelium
Summary
Whereas previous data has identified a large CD69 + NK cell population in the liver[10], data on CD8+ T cells with a tissue resident phenotype in the human liver is lacking, as is knowledge on their phenotype in patients with viral hepatitis. The aim of this study was to examine the presence of intrahepatic TRM in control patients without viral hepatitis, as well as the presence of these cells in the liver from patients who are chronically infected with HBV or HCV
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