{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T19:00:49Z","timestamp":1751137249602,"version":"3.37.3"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF18OC0033206"],"award-info":[{"award-number":["NNF18OC0033206"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003035","name":"Aase og Ejnar Danielsens Fond","doi-asserted-by":"publisher","award":["18-10-0700"],"award-info":[{"award-number":["18-10-0700"]}],"id":[{"id":"10.13039\/501100003035","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Objectives<\/jats:title><jats:p>In alcoholic hepatitis (AH), dysfunctional T lymphocytes may contribute to the high mortality from infections. T lymphocyte activation is governed by the expression of co-stimulatory receptors such as 4-1BB balanced by inhibitory receptors such as Programmed Death receptor 1 (PD-1). 4-1BB expression is unaccounted for in AH, while PD-1 is elevated. We characterized expression of 4-1BB and PD-1 and the associated T lymphocyte functional status in AH and investigated whether these were associated with short-term mortality.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>Thirty-five patients with AH (at diagnosis and days 7 and 90) were compared with healthy controls (HC). Spontaneous and<jats:italic>in vitro<\/jats:italic>stimulated receptor expression were quantified by flow cytometry, and plasma proteins by ELISA.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>At diagnosis, the patients showed increased stimulated 4-1BB responses of CD4<jats:sup>+<\/jats:sup>T lymphocytes. Also, the frequencies of PD-1<jats:sup>+<\/jats:sup>T lymphocytes both with and without co-expressed 4-1BB were increased. Further, interferon-gamma was predominantly produced in T lymphocytes co-expressing 4-1BB. A decrease in the frequency of spontaneous 4-1BB<jats:sup>+<\/jats:sup>T lymphocytes and an increase in soluble 4-1BB during the first week after diagnosis were associated with higher mortality at day 90 in AH. PD-1 expression showed no systematic dynamics related to mortality.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>We found an increased stimulated 4-1BB response of T lymphocytes in AH and early loss of these lymphocytes was associated with a higher short-term mortality. This suggests a role of T lymphocyte 4-1BB expression in the progression of AH.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0255574","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T17:33:57Z","timestamp":1628184837000},"page":"e0255574","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2610-2051","authenticated-orcid":true,"given":"Lotte Lindgreen","family":"Eriksen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten 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