Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3296776 | Gastroenterology | 2007 | 10 Pages |
Abstract
Background & Aims: Biliary atresia is an inflammatory, fibrosclerosing neonatal cholangiopathy, characterized by a periductal infiltrate composed of CD4+ and CD8+ T cells. The pathogenesis of this disease has been proposed to involve a virus-induced, subsequent autoreactive T cell-mediated bile duct injury. Antigen-specific T-cell immunity involves clonal expansion of T cells expressing similar T-cell receptor (TCR) variable regions of the β-chain (Vβ). We hypothesized that the T cells in biliary atresia tissue expressed related TCRs, suggesting that the expansion was in direct response to antigenic stimulation. Methods: The TCR Vβ repertoire of T cells from the liver, extrahepatic bile duct remnants, and peripheral blood of biliary atresia and other cholestatic disease controls were characterized by fluorescent-activated cell sorter analysis, and TCR junctional region nucleotide sequencing was performed on expanded TCR Vβ regions to confirm oligoclonality. Results: FACS analysis revealed Vβ subset expansions of CD4+ and CD8+ T cells from the liver or bile duct remnant in all patients with biliary atresia and only 1 control. The CD4+ TCR expansions were limited to Vβ3, -5, -9, and -12 T-cell subsets and the CD8+ TCR Vβ expansions were predominantly Vβ20. Each Vβ subset expansion was composed of oligoclonal populations of T cells. Conclusions: Biliary atresia is associated with oligoclonal expansions of CD4+ and CD8+ T cells within liver and extrahepatic bile duct remnant tissues, indicating the presence of activated T cells reacting to specific antigenic stimulation. Future studies entail identifying the specific antigen(s) responsible for T-cell activation and bile duct injury.
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Authors
Cara L. Mack, Michael T. Falta, Andrew K. Sullivan, Frederick Karrer, Ronald J. Sokol, Brian M. Freed, Andrew P. Fontenot,