التفاصيل البيبلوغرافية
| العنوان: |
Oligoclonal Expansions of CD4+ and CD8+ T-Cells in the Target Organ of Patients With Biliary Atresia. |
| المؤلفون: |
Mack, Cara L., Falta, Michael T., Sullivan, Andrew K., Karrer, Frederick, Sokol, Ronald J., Freed, Brian M., Fontenot, Andrew P. |
| المصدر: |
Gastroenterology (00165085); Jul2007, Vol. 133 Issue 1, p278-287, 10p |
| مصطلحات موضوعية: |
T-cell receptor genes, CLONE cells, BILIARY atresia, GLYCOPROTEINS, PATIENTS |
| مستخلص: |
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. [Copyright &y& Elsevier] |
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