Cruickshank S M, Southgate J, Selby P J, Trejdosiewicz L K
Research School of Medicine, University of Leeds, St James's University Hospital, UK.
J Hepatol. 1999 Dec;31(6):1026-33. doi: 10.1016/s0168-8278(99)80315-8.
BACKGROUND/AIMS: Human intrahepatic biliary epithelial cells can express immune recognition elements and are targets for immune attack in several liver pathologies. The aim of this study was to investigate the ability of biliary epithelial cells to act as accessory cells for T cell activation in normal and inflammatory conditions.
Normal biliary epithelial cells were cocultured with allogeneic unstimulated and mitogen- or antigen-stimulated peripheral blood lymphocytes. T cell responses were assessed by flow cytometry.
Biliary epithelial cells did not induce allostimulation in resting T cells and inhibited T cell activation in response to either phytohaemagglutinin, mitogenic anti-CD3 antibody or recall antigen, irrespective of the presence of accessory cells. Biliary epithelial cells did not affect T cell viability, promote or inhibit activation-induced apoptosis nor modulate expression of CD95/Fas. In presence of biliary epithelial cells, stimulated T cells failed to develop an antigen-committed (CD45R0hi) phenotype and were unresponsive to subsequent CD3 ligation. However, T cells underwent normal activation in the presence of biliary epithelial cells which had been pre-treated with Interferon gamma or TGFbeta, cytokines implicated in liver disease.
In normal liver, biliary epithelial cells inhibit rather than promote T cell activation, but their anergising effects may be overcome in response to trauma.
背景/目的：人肝内胆管上皮细胞可表达免疫识别元件，并且在几种肝脏疾病中是免疫攻击的靶标。本研究的目的是探讨胆管上皮细胞在正常和炎症条件下作为T细胞活化辅助细胞的能力。
将正常胆管上皮细胞与同种异体未刺激的以及丝裂原或抗原刺激的外周血淋巴细胞共培养。通过流式细胞术评估T细胞反应。
胆管上皮细胞不会在静止T细胞中诱导同种异体刺激，并且无论辅助细胞是否存在，均能抑制T细胞对植物血凝素、促有丝分裂抗CD3抗体或回忆抗原的活化反应。胆管上皮细胞不影响T细胞活力，不促进或抑制活化诱导的凋亡，也不调节CD95/Fas的表达。在存在胆管上皮细胞的情况下，受刺激的T细胞无法形成抗原定向（CD45R0hi）表型，并且对随后的CD3连接无反应。然而，在存在经干扰素γ或TGFβ预处理的胆管上皮细胞的情况下，T细胞可正常活化，这两种细胞因子与肝脏疾病有关。
在正常肝脏中，胆管上皮细胞抑制而非促进T细胞活化，但在创伤反应中其无反应作用可能会被克服。
