© 2002 SAGE Publications
Chimeric Liver Allografts Lack the Ability to Induce Spontaneous Tolerance after Orthotopic Liver Transplantation
Soluble major histocompatibility complex (MHC) class I antigens released from hepatocytesand the passenger leucocyte (PL) population of the liver allograft have both beenconsidered important contributors for spontaneous liver tolerance. This study was conductedto delineate the role of PLs in more detail. Whereas liver allografts of Dark Agouti(DA) donors were rejected in Lewis graft (LEW) recipients, orthotopic liver transplantationof LEW grafts in DA recipients induced spontaneous tolerance. Irradiated LEW liverswhere the PL population has been successfully eliminated loose their ability to survivein allogeneic DA hosts, whereas they survive in syngeneic hosts. Reconstitution ofirradiated LEW livers with syngeneic (but not with allogeneic) PLs restored tolerance induction.Despite this, tolerance induction liver chimerism was not related to long-termchimerism in DA recipients (spleen, thymus, and blood). Interestingly, PLs of LEW origincan also stimulate graft rejection of irradiated DA livers in syngeneic DA hosts. PLs playan ambiguous role as protectors of liver allografts. This phenomenon is not relying onthe induction of micro- or macrochimeric hosts. We speculate that the liver parenchymadetermines the dual function of PLs in liver transplantation. This work reveals the significanceof PLs as important contributors for spontaneous liver tolerance. Elimination ofdonor PLs results in graft rejection, whereas reconstitution of these cells restores toleranceinduction. Liver tolerance appears to be mainly induced in the graft itself, as thisphenomenon is not relying on the induction of micro- or macrochimeric hosts.
Key Words: spontaneous tolerance passenger leucocytes chimerism liver transplantation