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Cited by 79Liver physiology and pathologyT-cell and B-cell ImmunologyLiver Diseases and Immunity

Obstructive Jaundice Expands Intrahepatic Regulatory T Cells, Which Impair Liver T Lymphocyte Function but Modulate Liver Cholestasis and Fibrosis

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Katz, Steven C, Ryan, Kristin, Ahmed, Naseem, Plitas, George, Chaudhry, Umer I, Kingham, T Peter, Naheed, Seema, Nguyen, Cang +4 more·2011·The Journal of Immunology
DOI 10.4049/jimmunol.1004077PMC PMC3372324
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Abstract

Although obstructive jaundice has been associated with a predisposition toward infections, the effects of bile duct ligation (BDL) on bulk intrahepatic T cells have not been clearly defined. The aim of this study was to determine the consequences of BDL on liver T cell phenotype and function. After BDL in mice, we found that bulk liver T cells were less responsive to allogeneic or syngeneic Ag-loaded dendritic cells. Spleen T cell function was not affected, and the viability of liver T cells was preserved. BDL expanded the number of CD4+CD25+Foxp3+ regulatory T cells (Treg), which were anergic to direct CD3 stimulation and mediated T cell suppression in vitro. Adoptively transferred CD4+CD25− T cells were converted into Treg within the liver after BDL. In vivo depletion of Treg after BDL restored bulk liver T cell function but exacerbated the degrees of inflammatory cytokine production, cholestasis, and hepatic fibrosis. Thus, BDL expands liver Treg, which reduce the function of bulk intrahepatic T cells yet limit liver injury.

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References 42 · Cited by 79

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Authors
Katz, S. C., Ryan, K., Ahmed, N., Plitas, G., Chaudhry, U. I., Kingham, T. P., Naheed, S., Nguyen, C., Somasundar, P., Espat, N. J., Junghans, R. P., & DeMatteo, R. P.
Affiliations
  • Boston University (US)
  • Roger Williams Medical Center (US)
  • Memorial Sloan Kettering Cancer Center (US)
Corresponding author
Plitas, George
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2011-08-01
Volume
187
Issue
3
Pages
1150-1156
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.1004077
PMC
PMC3372324
OpenAlex
W1577562406
Cited by
79
References
42
Citations by year
2026: 1 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 2 · 2017: 8 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 7 · 2012: 3
FWCI
3.01
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (T32CA009501)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 068346, R01DK068346)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
obstructive jaundice, bile duct ligation, regulatory T cells, Foxp3, T cell anergy, cholestasis, liver fibrosis, liver injury, adoptive Treg transfer, Treg depletion, dendritic cell activation, inflammatory cytokines
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Cholestasis, Intrahepatic, Ligation, Liver, Liver Cirrhosis, Biliary, Liver Function Tests, Lymphocyte Depletion, Lymphocyte Activation, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, CD4 Antigens, Mice, Knockout, Jaundice, Obstructive, T-Lymphocytes, Regulatory, Mice, Interleukin-2 Receptor alpha Subunit

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