Biliary Atresia Is Associated with CD4+ Th1 Cell–Mediated Portal Tract Inflammation

Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia

“…It has recently been proposed that the perinatal/acquired form may be caused by a biliary trophic viral infection, leading to an initial bile duct epithelial injury that triggers a persistent immune-mediated sclerosing process resulting in obstruction of extrahepatic bile ducts [4]. In support of this inflammatory hypothesis, we have recently characterized the immunologic phenotype present within the portal tracts of infants with a variety of cholestatic liver diseases at the time of diagnosis [11]. That study demonstrated that the portal tract inflammation which was unique to BA was composed of a CD4 + Th1 cell predominant process, characterized by an infiltrate of CD4 + and CD8 + T cells and macrophages with local cellular production of IL-2, IFN-γ and TNF-α.…”

“…In human BA, we have reported that the portal tract inflammatory infiltrate is composed primarily of increased CD4 + and CD8 + T cells as well as a dramatic influx of macrophages surrounding intrahepatic bile ducts [11]. The immunophenotype of the inflammatory cells surrounding the bile ducts in the murine BA model was first determined by immunohistochemistry.…”

“…In human BA, we have shown that increased mRNA expression of all Th1 cytokines (IL-2, IFN-γ, IL12, TNF-α) was present at the time of diagnosis and that this expression was localized to cells residing in the portal tracts [11]. To determine if a similar CD4 + Th1 cellular profile of cytokines was present in the murine BA model, we determined cytokine protein and message levels.…”

Th-17 cells infiltrate the liver in human biliary atresia and are related to surgical outcome

“…Our initial immunohistochemical studies showed this to be predominantly CD4+ T cells and CD56+ NK cells with evidence of activation (CD25) and proliferation (CD71) (13). Later studies characterized this as a Th1 cell mediated portal tract inflammation (through production of IL-2, IFN-γ and TNF-α) (6). Such Th1 cell subsets were shown to be oligoclonal suggesting that the T cells in BA proliferate in response to a specific antigen, such as viral proteins, or even 'self' bile duct epithelial proteins (14).…”

“…Biliary Atresia Splenic Malformation syndrome (BASM) (5), or because the bile duct abnormality has structural changes making it detectable from the 16 th week of gestation (i.e. cystic biliary stresia) (6). More common are other infants, labelled as Isolated BA, who still may have primary developmental bile duct failure, but for which there is no clinical evidence.…”