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 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.
authors.affiliation: Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. skatz@rwmc.org
authors.forename: Steven C
authors.initials: SC
authors.lastname: Katz
authors.forename: Kristin
authors.initials: K
authors.lastname: Ryan
authors.forename: Naseem
authors.initials: N
authors.lastname: Ahmed
authors.forename: George
authors.initials: G
authors.lastname: Plitas
authors.forename: Umer I
authors.initials: UI
authors.lastname: Chaudhry
authors.forename: T Peter
authors.initials: TP
authors.lastname: Kingham
authors.forename: Seema
authors.initials: S
authors.lastname: Naheed
authors.forename: Cang
authors.initials: C
authors.lastname: Nguyen
authors.forename: Ponnandai
authors.initials: P
authors.lastname: Somasundar
authors.forename: N Joseph
authors.initials: NJ
authors.lastname: Espat
authors.forename: Richard P
authors.initials: RP
authors.lastname: Junghans
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Dematteo
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002780:Cholestasis, Intrahepatic / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D041781:Jaundice, Obstructive / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008026:Ligation / Q000009:adverse effects; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008213:Lymphocyte Activation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit