Obstructive jaundice expands intrahepatic regulatory T cells, which impair liver T lymphocyte function but modulate liver cholestasis and fibrosis Journal Article
| 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. |
| Article Title: | Obstructive jaundice expands intrahepatic regulatory T cells, which impair liver T lymphocyte function but modulate liver cholestasis and fibrosis |
| 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 Agloaded 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. Copyright © 2011 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; nonhuman; transcription factor foxp3; animal cell; mouse; cell viability; dendritic cell; animal experiment; animal model; in vivo study; in vitro study; regulatory t lymphocyte; adoptive transfer; cytokine production; immunomodulation; cd4 antigen; liver cell; disease exacerbation; cell expansion; t lymphocyte activation; lymphocyte count; lymphocyte function; interleukin 2 receptor alpha; spleen cell; bile duct ligation; intrahepatic cholestasis; liver fibrosis; obstructive jaundice |
| Journal Title: | Journal of Immunology |
| Volume: | 187 |
| Issue: | 3 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2011-08-01 |
| Start Page: | 1150 |
| End Page: | 1156 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1004077 |
| PROVIDER: | scopus |
| PUBMED: | 21697460 |
| PMCID: | PMC3372324 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 October 2011" - "CODEN: JOIMA" - "Source: Scopus" |
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