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CD161+CD4+ T cells are enriched in the liver during chronic hepatitis and associated with co-secretion of IL-22 and IFN-γ

Title: CD161+CD4+ T cells are enriched in the liver during chronic hepatitis and associated with co-secretion of IL-22 and IFN-γ
Authors: Kang, Yu-Hoi; Seigel, Bianca; Bengsch, Bertram; Fleming, Vicki M.; Billerbeck, Eva; Simmons, Ruth; Walker, Lucy; Willberg, Chris B.; Barnes, Eleanor; Bhagwanani, Anisha; Oo, Ye H.; Blum, Hubert Erich Christoph; Adams, David H.; Thimme, Robert; Klenerman, Paul
Source: Frontiers in immunology. - 3 (2012) , 00346, ISSN: 1664-3224
Publication Year: 2012
Collection: University of Freiburg: FreiDok
Description: Hepatitis C virus infection is a major cause of chronic liver disease. CD4+ T cells play a key role in disease outcome. However, the critical functions and associated phenotypes of intrahepatic CD4+ T cells are not well defined. We have previously shown that CD8+ T cells expressing the C type lectin CD161 are highly enriched in the human liver, especially during chronic hepatitis. These cells are associated with a type 17 differentiation pattern and express cytokines including IL-17A, IL-22, and IFN-γ. We therefore analyzed expression of CD161 on CD4+ T cells in blood and liver and addressed the relevant phenotype and functional capacity of these populations. We observed marked enrichment of CD161+CD4+ T cells in the liver during chronic hepatitis such that they are the dominant subtype (mean 55% of CD4+ T cells). IL-22 and IL-17 secreting CD4+ T cells were readily found in the livers of HCV+ and NASH donors, although not enriched compared to blood. There was, however, specific enrichment of a novel subset of IL-22/IFN-γ dual secretors (p = 0.02) compared to blood, a result reconfirmed with direct ex vivo analyses. These data indicate the dominance of CD161+ expressing lymphocyte populations within the hepatic infiltrate, associated with a distinct cytokine profile. Given their documented roles as antiviral and hepatoprotective cytokines respectively, the impact of co-secretion of IFN-γ and IL-22 in the liver may be particularly significant.
Document Type: article in journal/newspaper
File Description: pdf
Language: English
Relation: https://freidok.uni-freiburg.de/data/106387
DOI: 10.3389/fimmu.2012.00346
Availability: https://freidok.uni-freiburg.de/data/106387; https://nbn-resolving.org/urn:nbn:de:bsz:25-freidok-1063879; https://doi.org/10.3389/fimmu.2012.00346; https://freidok.uni-freiburg.de/dnb/download/106387
Rights: free
Accession Number: edsbas.18DBDA67
Database: BASE