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Tissue resident memory T cells (T RM ) have been identified in various tissues, however human liver T RM  to date remain unidentified. T RM  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 T RM , 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 T RM  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 T RM  which have a reduced cytolytic potential. In patients with chronic viral hepatitis T RM  have a distinct phenotype.

Human intrahepatic CD69 + CD8+ T cells have a tissue resident memory T cell phenotype with reduced cytolytic capacity