Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.
<h4>Objectives</h4>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 rece...
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oai:doaj.org-article:b6061a0c7b9a45bf8a299b67b9d94eab2021-12-02T20:18:37ZEarly loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.1932-620310.1371/journal.pone.0255574https://doaj.org/article/b6061a0c7b9a45bf8a299b67b9d94eab2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255574https://doaj.org/toc/1932-6203<h4>Objectives</h4>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.<h4>Methods</h4>Thirty-five patients with AH (at diagnosis and days 7 and 90) were compared with healthy controls (HC). Spontaneous and in vitro stimulated receptor expression were quantified by flow cytometry, and plasma proteins by ELISA.<h4>Results</h4>At diagnosis, the patients showed increased stimulated 4-1BB responses of CD4+ T lymphocytes. Also, the frequencies of PD-1+ 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+ 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.<h4>Conclusions</h4>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.Lotte Lindgreen EriksenMorten Aagaard NielsenTea Lund LaursenBent DeleuranHendrik VilstrupSidsel StøyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0255574 (2021) |
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Medicine R Science Q Lotte Lindgreen Eriksen Morten Aagaard Nielsen Tea Lund Laursen Bent Deleuran Hendrik Vilstrup Sidsel Støy Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis. |
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<h4>Objectives</h4>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.<h4>Methods</h4>Thirty-five patients with AH (at diagnosis and days 7 and 90) were compared with healthy controls (HC). Spontaneous and in vitro stimulated receptor expression were quantified by flow cytometry, and plasma proteins by ELISA.<h4>Results</h4>At diagnosis, the patients showed increased stimulated 4-1BB responses of CD4+ T lymphocytes. Also, the frequencies of PD-1+ 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+ 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.<h4>Conclusions</h4>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. |
format |
article |
author |
Lotte Lindgreen Eriksen Morten Aagaard Nielsen Tea Lund Laursen Bent Deleuran Hendrik Vilstrup Sidsel Støy |
author_facet |
Lotte Lindgreen Eriksen Morten Aagaard Nielsen Tea Lund Laursen Bent Deleuran Hendrik Vilstrup Sidsel Støy |
author_sort |
Lotte Lindgreen Eriksen |
title |
Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis. |
title_short |
Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis. |
title_full |
Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis. |
title_fullStr |
Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis. |
title_full_unstemmed |
Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis. |
title_sort |
early loss of t lymphocyte 4-1bb receptor expression is associated with higher short-term mortality in alcoholic hepatitis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doaj.org/article/b6061a0c7b9a45bf8a299b67b9d94eab |
work_keys_str_mv |
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