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T<jats:sub>RM<\/jats:sub> 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<jats:sub>RM<\/jats:sub>, of which a subset co-expressed CD103. CD69\u2009+\u2009CD8+ T cells expressed low levels of <jats:italic>S1PR1<\/jats:italic> and <jats:italic>KLF2<\/jats:italic> and a large proportion (&gt;90%) was CXCR6+, resembling liver T<jats:sub>RM<\/jats:sub> in mice and liver resident NK cells in human. Cytotoxic proteins were only expressed in a small fraction of liver CD69\u2009+\u2009CD8+ T cells in patients without viral hepatitis, however, in livers from CHB patients more CD69\u2009+\u2009CD8+ T cells were granzyme B+. In CHC patients, less intrahepatic CD69\u2009+\u2009CD8+ T cells were Hobit+ as compared to CHB and control patients. Intrahepatic CD69\u2009+\u2009CD8+ T cells likely T<jats:sub>RM<\/jats:sub> which have a reduced cytolytic potential. In patients with chronic viral hepatitis T<jats:sub>RM<\/jats:sub> have a distinct phenotype.<\/jats:p>","DOI":"10.1038\/s41598-017-06352-3","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T14:06:02Z","timestamp":1500300362000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Human intrahepatic CD69\u2009+\u2009CD8+ T cells have a tissue resident memory T cell phenotype with reduced cytolytic capacity"],"prefix":"10.1038","volume":"7","author":[{"given":"Femke","family":"Stelma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annikki","family":"de Niet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan J.","family":"Sinnige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel A.","family":"van Dort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaas P. 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Reesink serves as a consultant for AbbVie, Alnylam, Bristol Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck, PRA International, Regulus, Replicor, Roche and R-Pharm and received grant\/research support from AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Janssen-Cilag, Merck, PRA International, Regulus, Replicor and Roche. All other authors: None declared.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6172"}}