Cultured human biliary epithelial cells induce allogeneic lymphocyte activation in vitro: possible relevance in liver transplant rejection.

The biliary epithelium is a major target for allograft-directed immune responses during rejection crises after liver transplantation. This paper deals with in vitro studies on the immunogenetic potential of cultured biliary epithelial cells (BECs) to elicit an allogeneic cellular immune response. Therefore, BECs were cocultured with syngeneic and allogeneic lymphocytes in order to study lymphocyte activation. The respective lymphocytes [3H]thymidine incorporation was a measure for the proliferative activity. While syngeneic peripheral blood lymphocytes (PBL) never exhibited BEC-induced proliferation allogeneic PBL were significantly (P < 0.05) activated in all experiments (n = 6). In experiments with purified subpopulations CD8+ cells but not CD4+ cells proved to be activated by BECs. In time kinetics (n = 5) the maximum of the BEC-induced proliferation was on day 9 while the endothelial cell-induced proliferation was found to be 2 days earlier on day 7 after onset of the experiments (P < 0.05). BEC-induced proliferation was accompanied by induced IL-2 secretion (> 300 pg/ml) by activated lymphocytes as determined by ELISA. Stimulation of BECs with 500 U/ml interferon-gamma, 1000 U/ml interferon-alpha or blocking expression of HLA molecules on the surface membrane of BECs by monoclonal antibodies did not alter BEC-induced allogeneic lymphocyte proliferation. Monoclonal antibodies against CD8+ but not CD4+ suppressed proliferative activity of PBL and CD8+ cells by 40 and 45%, respectively. Overall, these results provide evidence that BECs may induce CD8+ lymphocyte activation in vivo and therefore might play a crucial role in triggering immune responses related to liver transplant rejection episodes.