Liver Non-Parenchymal Cells Induce Apoptosis in Activated T Cells in Vitro / 대한이식학회지

ABSTRACT

PURPOSE: Liver, unlike heart or skin, allografts transplanted between MHC-disparate mouse strains are spontaneously accepted without any immunosuppressive therapy. Despite the allograft acceptance, the recipients continue to exhibit donor-specific immune responses in vitro (MLR and generation of CTL). High levels of CTL apoptosis evident within tolerated liver grafts have been postulated as a mechanism underlying this 'split' tolerance. METHODS and RESULTS: By using radiometric DNA fragmentation test ("JAM" assay) and TUNEL staining, we present the evidence here that liver nonparenchymal cells (NPC) are quite strong inducers of activated T cell apoptotic death in allogeneic mice. This phenomenon occurs the similar level in activated T cells of syngeneic or third-party mice. Liver cells from gld (FasL-deficient) mice exert similar apoptosis-inducing effect on activated T cells from normal mice. Tumor necrosis factor receptor (TNFR) Fc fusion protein, and concanamycin A, an inhibitor of perforin pathway, fail to inhibit the apoptotic activity. CONCLUSION: These data indicate that liver NPC play important role in causing active apoptosis in graft-infiltratingCTL which favors liver graft acceptance, and liver-induced activated T cell apoptosis may not mediated by Fas, TNF or perforin pathways.