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

Human intrahepatic CD69 + CD8+ T cells have a tissue resident memory T cell phenotype with reduced cytolytic capacity.
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Stelma F, de Niet A, Sinnige MJ, van Dort KA, van Gisbergen KPJM, Verheij J, van Leeuwen EMM, Kootstra NA, Reesink HW,


Stelma F, de Niet A, Sinnige MJ, van Dort KA, van Gisbergen KPJM, Verheij J, van Leeuwen EMM, Kootstra NA, Reesink HW, (click to view)

Stelma F, de Niet A, Sinnige MJ, van Dort KA, van Gisbergen KPJM, Verheij J, van Leeuwen EMM, Kootstra NA, Reesink HW,

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Scientific reports 2017 07 217(1) 6172 doi 10.1038/s41598-017-06352-3
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.

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