J Korean Soc Transplant.  2001 Jun;15(1):73-78.

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

Affiliations
  • 1Department of Surgery, Hallym University College of Medicine, Anyang, Korea. yclee@www.hallym.or.kr
  • 2Thomas E. Starzl Transplantation Institute, University of Pittsburg Medical Center, Pittsburgh, PA, USA.

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.

Keyword

T cell apoptosis; Liver nonparenchymal cells; Immune tolerance; Transplantation
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