{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:28:33Z","timestamp":1790497713716,"version":"4.1.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T00:00:00Z","timestamp":1317081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>In primary biliary cirrhosis (PBC), patients develop a multilineage response to a highly restricted peptide of the E2 component of pyruvate dehydrogenase (PDC-E2) involving autoantibody and autoreactive cluster of differentiation (CD)4+ and CD8+ T-cell responses. Recent data from murine models have suggested that liver-infiltrating CD8+ cells play a critical role in biliary destruction in PBC. We hypothesized that chronic antigen stimulation of CD8+ T cells alters effector memory T cell (TEM) frequency and function similar to that seen with chronic viral infections, including failure to terminally differentiate and relative resistance to apoptosis. We have rigorously phenotyped CD8+ T-cell subpopulations from 132 subjects, including 76 patients with PBC and 56 controls, and report a higher frequency of TEM cells characterized as CD45ROhighCD57+CD8high, but expressing the gut homing integrin, \u03b14\u03b27, in peripheral blood mononuclear cells of PBC. These CD8high TEM cells have reduced expression of Annexin V after TCR stimulation. Consistent with a TEM phenotype, CD45ROhighCD57+CD8high T cells express higher levels of granzyme A, granzyme B, perforin, CCR5 and \u03b14\u03b27, and lower levels of CCR7 and CD28 than other CD8high T cells. Furthermore, interleukin (IL)-5 produced by CD8+CD57+ T lymphocytes upon<\/jats:bold>\n                                 <jats:bold>\n                                    in vitro\n                                 <\/jats:bold>\n                                 <jats:bold>T-cell receptor stimulation are increased in PBC. Histologically, CD8+CD57+ T cells accumulate around the portal area in PBC. Moreover, CD8+CD57+ T cells respond specifically to the major histocompatibility class I epitope of PDC-E2.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>In conclusion, our data demonstrate that CD45ROhighCD57+CD8high T cells are a subset of terminally differentiated cytotoxic TEM cells, which could play a critical role in the progressive destruction of biliary epithelial cells. (Hepatology 2011;54:1293\u20131302)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.24526","type":"journal-article","created":{"date-parts":[[2011,7,6]],"date-time":"2011-07-06T17:48:33Z","timestamp":1309974513000},"page":"1293-1302","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":63,"title":["Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis"],"prefix":"10.1097","volume":"54","author":[{"given":"Masanobu","family":"Tsuda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko 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